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viro3
virology
139
Veterinary Medicine
Graduate
04/10/2011

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Term
alpharetrovirus
Definition
ALV
Term
betaretrovirus
Definition
mouse mammary tumor virus, 8opvine pulmonary adenomatosis virus
Term
Gammatretrovirus
Definition
FeLV, FeSV, Murine leukemia virus, human leukemia virus
Term
Deltatretorvirus
Definition
BoLV
Term
Epsilonretrovirus
Definition
dermal sarcomas and hyperplasia (Walleyes)
Term
Lentivirus
Definition
HIV, FIV, SIV, EIA, CAEV (Visna (CNS)/maedi (lungs) virus; "maedi" = "slow")
Term
Retroviridae: simple (ie. gag, pol, env genes) v. complex genome )gag, pol env, AND genes coding for regulatory proteins)
Definition
Simple - alpha, beta, gammatretroviruses
Complex - delta, epsilon, lentiretrociruses
Term
T/F Retroviruses cause latent infections
T/F Retorviruses are very labile outside of the host
Definition
T
T
Term
Retrovirus replication
Definition
REVERSE TRANSCRIPTION w/in cytoplasm! -> enters nucleus & is now a "PROVIRUS" (ie. integrated dsDNA)

Some:
splice generating GAG-pol precursor (ie. structural genes = RT, Integrase)
Some -(read thru gag-pol)-> long polypeptide, cleaved -> RT & IT incorporated into virus (~1:20)
Some translation: move thru vesicles (Golgi, ER, CM) incorporated

Packaging
Egression
Term
requirements for international movement of dogs
Definition
proof of vaxx, VN test: RFFIT (Frapid flourescent focus inhibition test), FAVN (flouresecent Ab virus neuralizatoin test)
Microchip ID
Quarantine (1-6 mos)
Term
Simple v. Complex proviruses & antiviral targets & *excpetions
Definition
Simple- contains Pr (protease) = ANTIVIRAL TARGET
Gag-strucutral proteins (c0re)
pol = RT IN + Pr (enzymes)
envelope SU, TM
LTR = enhancers, promoters

LENTIVIRUS = lots of genes encoding for small regulatory proteins = ANTIVIRAL therapy
Term
Functions of some lentivurs regulatory proteins
Definition
vif: binds to and degrates APOBEC 3G protein (which is a part of intrinsic defense- incorporates into proten virions and interfese w subsequent relication
tat: transactivation of virus gene (tax- homologous gene of BoLV)
rev: export of viral RNA from nucleus
nef: down regulates CD4 recepotrs
Term
replication of competent vs. incompetent retroviruses
Definition
replication competant viruses = EXOGENOUS (can leave host) and are transmitted HORIZONTALLY (ie. FeLV, ALV, BoLV)
NOTE: ALV is passed VERTICALLY: congenital (chronic, leukemia) or provirus = genetic (latent, sometimes leukemia)

ENDOGENOUS (remains as provirus w/in host DNA) and transmitted GENETICALLY
these can be "rescued" by replicaiton competent viruses ie. exogenous FeLV/ednogenous FeLV (results in genetic changes of exogenous FeLV (ie. different subgroups) (ie. FeSV some FeLVs)
Term
Mechanisms of retrovirus oncogenesis: Insertional mutagenesis
Definition
Insertional mutagenesis/cis-activation - cell oncogenes come under control f provirus LTR w its strong enhancer and promoter elements ie. cis-activation
specific c-oncs can be disrupted by insertion of provurs, a random process ie. insertional mutagenesis - ie. responsible for the VARIABLE/RANDOM incubation time of FeLV in infected cats
Term
Mechanisms of Retrovirus replication (3)
Definition
insertional mutagenesis
transduction
transactivation
Term
Mechanisms of retrovirus replication: Transduction
Definition
Transduction - acquisition of a virus oncogene (v-onc) ie. a portion of a c-onc w/o its control elements:
conc products (oncoproteins) regulate cell activities including mitosis (c-oncoprotein production is controlled by a feed back mechansism; v-onc's cannot be regulated ie. NO feedback mechanism b/c they represent c-onc's w/o control elements)
essentially all retroviruses have the ability to acquire host DNA iee. oncogenes or other DNA (xenotropic retroviruses have the potential to transfer genetic elements w/in and btw species
Rous sarcoma virus is a classical example of a retrovirus that has acquired a v-onc: ACUTELY transforming retroviruses (v-onc expressed immediately once in host cell)

"Read through" + normal c-onc -> intramolecular recombination -> v-onc
Term
Mechanisms of retrovirus replication: Transduction
Definition
retroviruses encoded regulatory proteins that can affect cell growth activities ie. the transactivating genes TAX of BoLV & TAT of HIV
Term
FeLV model
Definition
subgroups: A,B,C,T - based on env gene & receptor specificity (aka "receptor usage")
FeLV-A represented in host w/ or w/o FeLV-B,C (subgroups FeLV-B & C arise de novo from recombination of env gene w/ engeogeous FeLVA (B &C responsible for CLINCIAL MANIFESTATIONS)
FeLV-B & C replication in hu cell cultures w/ no evidence of human infection (A DoES NOT REPLICATE in hu cell cultures)

ontogeny:
day 0 = FeLV-A infection
Primary viremia: Targets lnn, spleen, IT UB, Salivary gl, bone marrow
Day 7-14: Seoncdary Viremia
Shedding
**Immune response may terminate infection (<16 wks) o r= PI if >16 wks(mos - yrs?)
Term
FeLV dz manifestations
Definition
Lymphosarc: multicentric, thymic, alimentary, invasive Tcell tumors in non-lymphoid tissue (CNS, skin, eye)
Myeloproliferative dz & anemia: : erytheatic myelosis (erythroid progenitor cells), granulocytic leukeia (myeloid progenitor cells)
Immuno-pathogenic dz: immune complex(ie. GN (rare)), immuno suppressin:(decr in T cells (CD4, CD8) B cells & myeloid cells - enhancement of FIP herpes crypto, Mycoplasma infections; slow wound healing, gingivitis, chronic respiratory dz, etc)
Fibrosarc: (rare) multifocal s.c. in young kittens, induced by FeSV but requires FeLV-A as helper
Term
Why so many FeLV dz manifestations?
Definition
FeLV-A strains assoc w marked immune suppression: have specific env mutation
intramolecular recombination of FeLV-A w endogenous FeLV-A & other retrovirus elements in host DNA + mutation generate: FeLV-B assoc w THYMIC LYMPHOSARC & FeLV-C assoc w SEVERE APLASTIC ANEMIA

Determinants of virulence/dz manifestation:
1. site of provirus insertion -> disregulationof specific c-onc genes (6 loci) - ie. thymic vs.alimentary lymphosarc
2. Mutations in env/SU -> utilization of different receptors
3. LTR variability btw isolates
Term
Dx: FeLV testing
Definition
1. Ag capture ELISA: positive test mayor maynot mean PI but likely if positive >16 wks
2. Direct FA detects AG associated w/ neutrophils and plts in unfixed blood semars - positive test indicates probable PI as it generally becomes positive ~3 wks after initial infection
3. RT-PCR (tests viral nucleic acid, RT)
Term
FeLV Control/Vaxx
Definition
Killed
*Canarypox recombinant -> SU = VAXX TARGET (=Anti-R & keeps virus from getting into cell) - serogroups are determined by specificity to SU glycoprotein
Term
FeSV model: Rescue by FeLV
Definition
1. cel w replication imcompetent FeSV
2. co-infection w/ FeLV that contains genes for replication
3. progeny FeLV & FeSV released. FeSV free to infect susceptible cell. v-onc expressed if provirus inserts into ACTIVE area
(FeSV acquires envelope of FeLV - required for replication)
Term
challenges of antiviral drugs
Definition
1. timing (viruses typically have done significant damage before their presence is recognized) - countered by rapid dx & prophylacti antiviral drugs
2. Drug-resistant mutants arise quickly (minimized by use of drug combos ie. HIV)
3. Safety -viruses are obligate parasites and use many o the same physiological pathways of the cell, thus toxicity is an issue (ID ts in virus replication cycle that are unique to the virus whenever possible ie. vRNA dRNApol, cap snatching, etc)
Term
Nucleoside analogs: Herpesviruses
Definition
IDU (5'-iodo-2'-deoxyuridine) - topical tx of herpetic corneal ulcerts today derivatives of acyclovir are more commonly used (topical: cidofovir, systemic: famciclovir)
2. Ara-a (adenine arabinoside) - first parenteral effective against HSV VSV
3. Acyclovir: chain terminator
1. inhibits vDdD (significalntly higher 2. affinity for vDdD than cDdD)

a "prodrug" that is activated by herpesvirus **thymidine kinase in virus infected cells

The Beta-herpesvirinae ie. cytomegalo viruses do NOT encode viral th kinase but have kinases capable of phosphorylating the acyclovir derivative, gancyclovir

(Acyclovir -(th kinase)> Acyclovir monophosphate -(cellular kinase enzymes)> acyclovir triphosphate -(viral polymerase)> incorporated into replicating vDNA (& cDNA)) -> CHAIN TERMINATION

relatively poor bioavailability therefore most useful for topical tx; Valtrex "prodrug" used sysntemically (valine enhances uptake from gut)
Term
Nucleoside derivatives: Acycloviru
Definition
3. Acyclovir: chain terminator
1. inhibits vDdD (significalntly higher 2. affinity for vDdD than cDdD)

a "prodrug" that is activated by herpesvirus **thymidine kinase in virus infected cells

The Beta-herpesvirinae ie. cytomegalo viruses do NOT encode viral th kinase but have kinases capable of phosphorylating the acyclovir derivative, gancyclovir

(Acyclovir -(th kinase)> Acyclovir monophosphate -(cellular kinase enzymes)> acyclovir triphosphate -(viral polymerase)> incorporated into replicating vDNA (& cDNA)) -> CHAIN TERMINATION

relatively poor bioavailability therefore most useful for topical tx; Valtrex "prodrug" used sysntemically (valine enhances uptake from gut)
Term
IV: M2 & HA targets
Definition
Amantadine:
mode of action: UNCOATING
low dose affects M2 ion channel and only affective against Type A influenza
high dose acts as a high base (increases pH w/in endosome interfeering w/ pH-dependent membrane fusion, effective against type A which has M2 channel, types B & C IV that do Nnot
*also inferferes w/ maturation of HA as it is processed in cell secretory pathway

Resistant mutants arise quickly
CNS side effects (crosses BBB!)
Methylated derivative aka Rimantadine does NOT cross the BBB
Amantadine also used to alleviate symptoms of Parkinson's
Term
IV: NA target
Definition
NA interacts w/ SA residues on cell surface & prevents progeny virus from "pilling up" on CM during release
enzyme active sites of NA are highly conserved, thus virus mutants occur less requently than amantadine-induced mutants

NA inhibition via:
Zanamivir (ihalation)
Oseltamivir (oral)
mode: derivatives of SA w/ greater affinity for the NA enzyme active site than SA
Term
Picornavirus: antiviral drugs
Definition
Peconaril - onl for Enterovirus Encephalitits
blocks access to receptor bining site ni the floor of canyon
experimentally effective against Coxasackie & Thinoviruses
Term
Retrovirus: antiviral drugs
Definition
attack RT (virus specific)
Proteases- chop Gag, pol etc = inhibit IT -> interferes w/ viral replication
HIV
LTR
all dependent on protease for production of RT & IN

Nucleoside analogs:
AZT for HIV: RT inhibitor/chain terminator (affinity of AZT for RT is ~100x > than dTTP; incorporated into viral DNA by reverse transcriptase
side effects common
multiple mutations in pol gene

Protease inhibitors:
Ritnovir, Sasquinavir, Indinavir, Nelfinavir (several)
mutations arise quickly
side effects are common : ritonavir, sasquinavir, have chymotrypsin-like effect on proteasome thus interfering w MHC-1
Term
HIV: antiviral drugs
Definition
LTR
all dependent on protease for production of RT & IN

Nucleoside derivatives: AZT:
RT inhibitor/chain terminator (affinity for AZT for RT is ~100x > than dTTP, incorporated into viral DNA by RT)
side effects common
multiple mutations in pol gene

Protease inhibitors:
Ritonavir, Sasquinavir, Indinavir, Nelfinavir (several)
mutations arise quickly
Side effects common: ritonavir, sasquinavir have chymotrypsin-like effect on proteasome thus interfering w/ MHC1

Integrase inhibitors:
Raltegaravir - Reverse transcribed product, vDNA cannot be integrated into host DNA
Term
Other antiviral drugs: Cidofovir
Definition
Phosphorylated acyclic nucleoside anaglog
initial phosphorylation by viral tk not required*
phosphorlyation to triphosphate form completed by cell kinases
*broad spec for DNA & Retroviruses
topica, IV, oral
Term
Other antiviral drugs: Ribavirin
Definition
nucleoside anaglog
interferes w/ "capping" of mRNA
decreases GTP pool in cell
interferes w/ RNAdRNApol

toxicity is a problem
used for Lassa Fever Hantavirus, Human RSV
Term
Other antiviral drugs: INFs
Definition
use for Hepatitis C in humans
FIP, FIV, FeLV but efficacny not proven
Term
Addressing the viral mutant issue
Definition
Drug coktails (ie. 2 (+) antivirals w/ differing targets

Atripla - combo of 1 nucleoside, 1 nuclotide, 1 non-nucleotide RT inhibitorSm
Term
Small interfering (si) and micro (mi) RNAs
Definition
miRNAs in mammalian cells generated from RNA associated with specific genes in nucleus: used in post-transcriptional regulation
siRNAs are generated from viral RNA - interfere w/ host cell defense
si & miRNAs are ~13-20 nucleotides long linked to endonucleases (RISC) - si & miRNA-RISC (RNA induced silencing complex) bind & degrade target mRNA

Application of siRNAs: prevent and successfully treat RSV & PI3 using siRNA that target mRNA for a protein of the polymerase complex
Term
Oncolytic viruses
Definition
NCD - Csartary LK - effective in lab experiments against malignant glioma in mouse model; effective in some human trials
Kills cancer via lysis and/or initiating apoptosis; effectiveness enhanced by inserting genes for IL2, NS1 and "highly fusogenic" F protein

ASENOVIRUSES - contitionally replicative ie. early genes removed (used for head & neck cancers glimoas others)

VSV - replication competent, effective in mouse model administered IV (glimoas & metastatic carcinoma in brain)
Term
Oncolytic viruses w/ "pro-drugs"
Definition
Retrovirus model & work of K Culver in viral therapy for cancer
- developed a retrovirus vector (RV) arrying the HSV tk gene - establisha rat glimoa cell model, inject RV tumor at multiple sites, inactivate form of an acyclovir derivative, gancyclovir then administer IV: brain tumor eliminated or development suppressed
Requirements: plasmid containing retrovirus construct with GOI ie. HSV1 gene, tk
a packaging cell encoding all components of a replication competent retrovirus but w/o the packaging sequence

HSV - conditionally replicative w/ GOI (CYP2B1); virus kills cancer via:
1. Lysis &
2. activating a parenterally administered inactive form of cyclophosphamide by the CYP2B1 gene product (note: CYP2B1 prevents cell devision by cross-linking DNA strands)
Term
Use of viruses in gene therapy
Definition
Viral vectors (DNA, RNA) can be used in tx of genetic disorders by introducing GOIs into target cells
Examples: Retro, adeno deno-associated viruses (dependovirus, parvoviridae), Herpes
Term
considerations in choosing a gene for gene therapy
Definition
1. size of GOI & capacity of vector genome
2. target cells: susceptibility to infeciton, terminally differentiated or actively dividing?
3. can virus vector be engineered to carry out function with minial injury to host?: immune response ie. will host develop AB to vector, develop an exuberant inflammatory response?
4. Insertional mutagenesis and gene slicing
Term
Retroviruses in gene therapy
Definition
effective vectors but require DIVIDING CELLS for max efficiency ie. not suitable for dzs such as cystic fibrosis;
Insertional mutagenesis & gene slicing are potential problems: Murine LV vector developed to tx SCID (servere combined immunodeficiency) in humans - tx successful but 4:10 principles developed leukemia due to insertional mutagenesis
Term
Adenoviruses in gene therapy
Definition
ie. Cystic fibrosis
target = mucus secreting cells of Respiratory tract
adenovirus engineered to be replication incompetent and contain the human CFTR gene (ie. GOI)
GOI is episomal effects of txs are short-lived
Issues: Repearted txs raise neutralizing Ab to virus vector
immune response to viral protein can induce inflammation
Term
AAV (Adeno-associated viruses) gene therapy
Definition
AAV being develop for variety of genetic disorders ie. Cystic Fibrosis Huntingtons Dz
GOI is primarily episomal but can integrate into cell DNA thus tx by AAV has the potential for a longer effect than tx adenoviruses
used not only to supply a normally functioning gene ie. "gene conditioning" but also to correct a defective gene "gene correction" ie. the "Holy Grail" of gene therapy
Issues: same as w/ adenoviruses but have advantage of being smaller virus (ie. less protein); insertional mutagenesis
AAV appear to integrate selectively at chromosome 19*


untington's dz: engineered AAV to: express Anti-receptor on capsid to target neurons expressing Huntingting protein (HP); generate miRNAs specific for mRNA of HP
Term
Families of viruses that induce oncogenesis
Definition
Papilloma (carcinoma of hu genital tissue, transform by some bovine & rabbit viruses
Polyoma (SV40 ~Polio vaxx & risk of infection)
Adeno (some)
Hepadna (Hep B: Liver cancer)
Herpes : (EBV, Burkits lymphoma, MDV)
Term
General characteristics of Papova & Polyomaviruses
Definition
small naked virions w/ icosahderal symmertry
genome is ds circular, only 1 strand is transcribed in Papilloma, both in Polyoma: papilloma do NOT replicate in cell culture
Papilloma: wart viruses: some app types transform cells, evlove to carcinomas ie. hu cervical carcinoma
Polyoma: Budgerigar Fledgiging dz: a generalized dz w/ high mortality, suspect "French molt" w/ feather defect also caused by this virus - affected fledgelings show weakness, pallor, s.c. hem, dehydrated, off feed, crop stasis (extended), death (30-80% mortality) - survivors shed virus in feces ~6 mos.
progressive multifocal leukoencephalopathy in immunosuppressed rhesus macaques (SV40) & humans (JC virus)
various solid turmos including SV40 in newborn rodents
Term
replication of polyomavirus
Definition
genome is too small to encode all proteins/enzymes that are required for replication - cell is induced by early gene products* of virus to prepare for mitosis which generates DdDpol and other compnents required for replication: early gene products "T" Ags of polyomaviruses & E5,6,7 gene products of papilloma interact w/ cell tumor suppressor proteins ie. pb53, Rb which have a role in regulating cell growth
Term
Functions of T Ags
Definition
binds w/ pb53/Rb
cell prepares to undergo division
cell produces:
1. DNA binding proteins
2. cell DdDpol
4. ribonucleotide reductase
Term
Functions of T Ags
Definition
binds w/ pb53/Rb
cell prepares to undergo division
cell produces:
1. DNA binding proteins
2. cell DdDpol
3. ribonucleotide reductase

When T reaches a critical level in the cytoplasm some T moves back into nucleus & binds to promoter region of its gene - production of mRNA specific for T is terminated
T also opens circular dsDNA which permists binding of cDdDpol to viral DNA and subsequent production of vDNA for progeny virions: simultaneously T facilitates expression of late genes that code for structural protein
Term
Traditional vaxx
Definition
whole inactivated, replicating (wild, attenuated)
Term
New generation vaxx
Definition
subunit/split/viral like particles, molecularly altered live, vectored, chimeric, viral replicon particles DNA
Term
New generation vaxx
Definition
subunit/split/viral like particles, molecularly altered live, vectored, chimeric, viral replicon particles DNA
Term
routes of administratino by virus
Definition
injection
eye drop - NCD
Aerosol - IBV
drinking water - IBV, NCD
Feed - NDV (regions where "cold chain" cannot be maintained
In ova - MD
Scarification - Orf, Fowl pox
Intranasal - Equine IV, BHV1, FIP
Term
Whole inactivated virus
Definition
inactivated by formalin, gluteraldehyde, beta priopiolactone (rabies), ethylenemine (FMDV)

potential problems: failure to inactivate all virus, loss of immunogenicity
adjuvanated ie. aluminum hydroxide
Term
Live virus vaxx
Definition
wild type via unnatural route: SMALL POX: variolation, skin v aerosol
ORF (axilla), FOWLPOX (web wing) scarification

WIld type used in heterologous host:
COWPOX immunization of hu for SMALLPOX
TURKEY V for MAREKS
PIGEON POX for FOWLPOX by skin scarification

Attenuated viruses ie. MLV for CDV
naturally occuring attenuated ie. Bartha's K strain of PRV
serially passaged through unnatural host (cell culture, eggs, animals)
Term
SUbunit/split vaxx, viruslike particles
Definition
Subunit (SU) or "split vaxx" contain 1(+) viral proteins but not all
the "DIVA" (differentiating infected from vaccinated animls) approach to dz control:
DIVA requires companion Dx tests for Ab to Ag NOT included in the vaxx
ie. an experimental vaxx developed for PRV (ISU) used envelop glycoproteins for SU vaxx and non-envelip proteins for Dx Ag
others: Hu IV split vaxx prepared by enzymatically cleaving HA from virus envelope

Virus Like Particles (VLP - recombinant self assemble into structural units forming capsids w/ nucleic acid
ie. hu genital papilloma virus vaxx
*Aleutian dz VLP - parvo virus - mink- recessive gene0defect in macrophages: affects ability fo macrophages to eliminate/destroy viral Ag/Ab complexes; virus retains infectivity; lots of Ab & Ag production -> GN
Term
Expression systems used in producing vaxx Ag
Definition
Baculovirus: insect virus w/ a very powerful promoter/enhancer for the polyhedrin (PH) gene:
GOI cloned into PH gene
insect cells or Lepidoptera caterpillars infected w/ virus

Yeast: used in production of Hep B vaxx Ag
E. coli
Eukaryotic cells
Transgenic plants for oral vaxx Ag (ie. NOROVIRUS)
Term
Molecularly altered live vaxx virus
Definition
deletion mutant/marker vaxx: 1(+) non-essential, highly antigenic viral proteins are deleted from vaxx candidate
ie. gE of BHV-1 vaxx, permits DIVA approach (ie. DIVA = IBR, PCV)

Temperature senstiive (ts) mutants ie. *"cold adapted": replication restricted to ~33oC URT
induce a balance immune response w/o causing systemic dz or repro losses
ie. IBR (aka BHV1), FIP
Term
Vectored vaxx virus
Definition
Vectored vaxx viruses are designed to infect a host w/o ill effect & carry a gene representing another virus to which immunity is desired
ie. VACCINA w/ Rabies G protein for immunizatino of wildlife population ie. raccoons
ie. CANARYPOX recombinat vaxx for: RELINE RABIES, FeLV, CDV, WNV

Construction of vectored vaxx:
1st virulence genes of the candidate virus vectorare ID's & neutralized/eliminated
GOI is cloned & inserted into a plasmid vector
ie. VACCINIA, CANARYPOX, ADENOVIRUS, HERPESVIRUS
Term
Chimeric viruses as vaxx
Definition
two closely related viruses in which one serves as the backbone w/ replication associated genes and the other providing one(+) genes encoding protiens to which an immune response is desired
ie. Chimeri-Vax JE: backbone = YFV, immunogenic = JE
ie. PCV2 (PVC1 serves as a backbone) PCV2 contributes genes for capsids*
Term
Virus Replicon Particles (VRP)
Definition
VRPs are replication defective viral particles that contain 1(+) GOIs
vaxx proteins expressed by GOIs processed by exocenous & endogenous pathways ie. balanced immune reponse
ie. Hu IV, CMV in hase I or II;
ie. PRRS & SIV
VEE (*alphavirus)
Term
DNA vaxx
Definition
plasmid contructs: can be coated onto gold particles and delivered into skin by "gene gun" or injected naked into skin or muscle
particles processed by APCs ie. Langerhan cells
Issues: Induce CMI, humoral (IgG), secretory (IgA) immune response
safety: some concern for insertiona mutagenesis, autoimmunity to DNA

DNA vaxx candidates:
WNV-Innovator DNA vaxx - no published data
H5N1 AI: IM or ID(intradermal)
EIV: liposomes: intranasal
Term
Dx Lab: BSLs
Definition
BSL1: agents w/ NO dz threat to humans
BSL2: agents capable of infecting humans by infestion, mucous membranes, sharpes (ie. salmonella)
BSL3: agents w/ serious & lethal consequences & transmitted by aerosol (ie. Hantavirus)
BSL4: highly lethal domestic/exotic agents transmitted by aerosols or unknown means (ie. Ebola, Hendra, Nipah viruses)
Term
Oversight for animal use & safety
Definition
IACUC (institutional Animal Care & Use Committee - labs using animals in xs or research
IBC (Institutional Biosafety Committee) - Lab safety overseen
Term
Sample collection
Definition
Pachecko's & poloma virus dz of psittacines - herpesvirus, & polyomavirus in the LIVER
EEE in brain but NOT blood when neuro signs present
BRSV difficult to isolate from dead animal (very labile)
Rota shed in greatest quantities (>10^9 particles/g) during first 3-4d of illness, then rapidly declines
Term
Psittacines: Gross & histo lesions
Definition
Budgerigar: polyomavirus - basophilic INIB but not clearly visible (whole virus)
Conure: Pacheko's dz (herpesvirus) = acidophilic INIB present, also stained Ag (viral particles)
Term
Sample collection II
Definition
aborted fetuses - focal necrosis, INIB in liver indicative of herpesvirus ie. EHV1, BHV1
PPV = PPV Ag in fetal lung
WNV/dead crows = virus in brain, also oral cavity, cloaca and feather shaft
Term
Virus isolation & ID
Definition
VI in embryonating eggs, cell culture, and animals
ID - serum virus neutralization (SVN) is Gold Standard (others: Fa/IFA, ELISA, HI, CF, PCR)\


tissue examples: BT (bovine turbinate for Bovine Resp viruses,
MA104 & derivative MARC-145 for PRRS (monkey kidney);
fetal equine liver aborted late gestation = EHV1
Term
NI (neutralization index)
Definition
the difference in logs btw end pts of control (normal, Ab-free serum) & test (Ab-pos) serum

*NI of 4(+) is considered pos for most viruses!
Term
Ag capture ELISA
Definition
FeLV model
Term
Demonstrating viral Ag in tissue by IHC
(examples)
Definition
TGE: villi of gut
PRRS: lungs of pigs
Parvo: lungs of fetal swine
Rabies: brain
PRV: palatine tonsils
CDV: conjunctiva & vaginal impression smears
Term
Demonstration of virus by EM
Definition
Sensitivity and specificity of neg staining can be incr by immuno-electron microscopy ie. adding virus specific Ab to sample prior to pelleting
Term
EM neg staining examples (by clinical symptoms)
Definition
viruses causing vesicular dz in cattle/swine: FMD, VSV, Bovine mammalitis, Pox

Enteric dz: Rota, Corona, Norwalk
Term
PCR & representation differential analysis (RDA)
Definition
RDA, a PCR techniques useful in IDing unknown pathogen uses RANDOM primers: NA extracted from normal tissue & dz'd tissue
PCR is run w/ random primers: amplicons appearning in dz'd, but NOT normal tissue may represent NA of unknown pathogen
Term
Serological ID of virus infection
Definition
Detection of IgM (recent infection) or IgG in previously naive animals
Demonstration of rising titer (4-

(*Reciprocal of dilution (ie. 1:16 = 16))fold (+) increase) over a 10-14 d period
Term
Specific serological tests
Definition
SVN
ELISA (IgM, IgG)
Agarose gel diffusion ie. COGGINS TEST for EIA
HI
CF
Term
SNV for detecting and quantifying AB
Definition
Note: SVN can be used to ID isolated viruses using known Ab or used to assay for specific Ab as by using known viral Ag

1. serum to be assayed is serially diluted in 2-fold increments, and constant amounts of each dilution added in duplicate to wells in microtiter plate
2. constant amount of known live virus added to each well
3. serum/virus incubated @ 37oC ~1 hr & cells are added
4. MP wells examined for presence or absence of virus activity @ ~3 d



2^x = titer (ie. 2^6 = 64)
Term
SVN for virus ID
Definition
1. unknown virus
2. virus specific Ab
3. to determine add cells (CPE = no SVN, normal cell monolayer = SVN)
Term
SVN; titers
Definition
if increase ID virus -> LOWER titer & DECREASED sensitivity

If decr virus ID -> Sensitivity would be DECREASED

*NOTE: Specificity is INVERSE of Sensitivity!!!!
Term
Hemagglutination Inhibition: Ab
Definition
used with viruses that have proteins taht agglutinate RBCs ie. IV, some PI viruses, flaviviruses, some Parvo, etc
HI can be used like SVN to ID viruses or detect Ab: HI differs from SVN in that it uses a different indicator system for detecting Ag, Ab interaction

same as SVN but inhibition of HA vs. CPE determines if Ag/Ab reactions occured
Virus + RBCs -> Mat = agglutination
Virus + Ab + RBCs -> button = NO agglutination

HA activity is relative NOT absolute as in quantifying virus infectivity (ie. ID50s/ml)
Term
Complement Fixation
Definition
like SVN is used to ID virus or detect Ab - difference is the indicator system used to detect Ag, Ab interaction

Test syetme: Ag, free C' (guinea pig serum), heat inactivated test serum (destroys any pro C' activity)
Indicator system: RBCs, Ab specific for RBCs (hemolysin)

Test system:
If Ab is present it will bind to Ag & fix C'
If absent -> Ag + free C'

Indicator system:
RBCs lyse only in presence of free C' & anti-RBC serum
Test system: no fre C' -> Indicator system: RBCs reamin intact
Test system: Free C' -> indicator ystem: Lysis of RBCs
Term
Agar gel diffusion test
Definition
ie. Coggins for EIA
Term
ELISA for detecting Ab
Definition
similar format used for ID WNV infeciton in horse.
1. Ab on plate is treated w/ WNV Ag
2. IgM in horse serum will bind to Ag & be detected by labeled 2o Ab
Term
hemagglutination Inhibition: Ag
Definition
HA activity is designated as # of HA units/unit vol
HA titers of stock preparations are relative b/c different assay conditions give different results
Term
Rabies background
Definition
major hosts: Canidae, Felidae, Mustelidae, Procyanidae, Viverridae, Ciroptera

Endemic w/ exceptions: AUS, New Zealand, Great Britian, Ireland, Hawaii, Japan

Rabies cases in USA predominantly in wildwilve (90%) & domestic animals (10%), human cases in US are rare but ~ 50000 WW
species distribution: raccoons > bats > skunks > fox > cats > dogs > cattle
cases in sheep, goats, horses & mongoose
Rabies in swine, rodents, squirrels is RARE
Term
Rabies background II
Definition
Wild type = "street"
attenuated = "fixed"
stability in environnment is variable
negri bodies

"anti-messenger" group (- polarity)
Term
Rabies classification: Rhabdiviridae
Definition
*Vesiculoviurs (VSV, fish viruses)
ephemerovirus (bovine ephemeral fever)
novirhabdovirus (infectious hematopoietic necrosis virus in salmonids, viral hemorrhagic septicemia virus, snakehead virus)
*Lyssavirus (rabies, bat lyssavirus)
unclassified (mostly fish viruses)
Term
Genus Lyssavirus
Definition
7 genotypes designated by number and based on % nucleotide homology and aa sequence of the N protein
4 proposed genotypes: Aravan, Irkut, Khujand, and West Caucasian bat virus


1 classical rabies virus
2 bat rabies virus
3 Mokola virus
4 Duvenhage virus
5,6 European bat lyssaviruses 1 and 2
7 Australian bat lyssavirus

Genotypes 1,3,4,5,6,7 cause hu dz (all but 2)
genotypes subclassified into biotypes (species specific)
Term
Genus Lyssavirus
Definition
7 genotypes designated by number and based on % nucleotide homology and aa sequence of the N protein
4 proposed genotypes: Aravan, Irkut, Khujand, and West Caucasian bat virus


1 classical rabies virus
2 bat rabies virus
3 Mokola virus
4 Duvenhage virus
5,6 European bat lyssaviruses 1 and 2
7 Australian bat lyssavirus

Genotypes 1,3,4,5,6,7 cause hu dz (all but 2)
genotypes subclassified into biotypes (species specific)
Term
Rabies virus biotypes
Definition
RV biotypes circulate in specific animal populations - species vary in susceptibility to biotypes
Biotypes are distinguished by differences in nucleotide sequences in G GENE, and/or G-L region (minor differences also in N gene)
Variants w/in biotypes are distinguished by MAB (monoclonal Ab) panels specific for N PROTEIN & nuceotide sequencing
Term
Bat biotypes & species
Definition
Little Brown bat
Silver-haired bat
Term
Summary of Rabies pathogenesis
Definition
entry via bite
replication in myocytes followed by entry into PNS thru ACH R & axonal movement to CNS where other Rare uilized
CNS:
limbic system involved fist (loss of cortical control ie. furious form),
neocortex (drum, paralytic forms)
death via Respiratory arrest but NOT prior to CENTRIFUGAL SPREAD to peripheral organs ie. Salivary gls

movement from CNS by peripheral nerves to internal organs, cornea, salivary gl, nerve bundles of sensory hairs
virus can be in saliva up to 10 ds before overt signs - >10d quarantine period in bite cases
Term
Rabies Clinical presentation
Definition
1. exposure via bite/scratch,IP 2-3 wks to 6 mos, *yrs
2. change in temperment, animal does things it normally doesnt ie. loss of fear of humans by wildlife
3. furious from ie. aggressive behavior, fursion leading to "dumb, paralytic" form, or just dub & paralytic form. *Death w/in ~2-14 d

additional overt signs: cannot swallow, protrusion nictitating mebrane, ptyalism, hyperstheia, self mutliation, pica, changes in vocalization
Term
Dx: Rabies
Definition
presumptive - abnormal behavior
Definitive: FAT on brain smear impression: brain stem, cerebellum, hippocampus, excellent site
- if neg then sucking mouse IC inoc test (MIT) & observe 21-28 d: FAT on brain smears of mice w/ CNS signs including death

Potantial alternatives to MIT
a. VI using BHK or Neuroblastoma cells & subsequent ID ie. FAT
b. RT-PCR: used w/ some success on samples not suitable for FAT, pos test meaninful but neg NOT

4oC, 50% glycerol in saline preserves brain where "cold chain" cannot be maintained
Term
Rabies Control
Definition
1. population mmgt - animal control, vaxx
2. dogs, cats - killed vaxx in US, Canada:
canarypox vectored feline rabies liscensed for cats
MLV: low & high egg passage still used in some countries but NOT USA (safety reasons)

Wildlife species
1vectored vaxx (oral): modified vaccinia virus containing rabies virus gene "G" that encodes the envelop glycoprotein - used successfully in baits for oral vaxx of raccoons, coyotes in US
Term
Rabies: Requirements for international movement of dogs
Definition
proof of vaxx
VN test (some countires req 2 consecutive tests at 12 wk intervals):
i. RFFIT (rapid flourescent focus inhibition test)
ii. FAVN (flourescent Ab virus neutralization test) ~OIEKSU VDL

Microchip ID's by Australia, Hawaii, New Zealand, St Kitts-Nevis
Quarantine req upon arrival varies (1-6 mos)
always check reqs at consulates for each country
Term
Vector-borne encephalitides
Definition
WEE, EEE, WNV, SLEV, LACV, VEEV, JEV, TBE & Louping Ill

WEE/EEE/WNV/SLEV = Cx & amplifying hosts = birds

Favi- WEE, EEE, SLEV, JEV, TBE & Louping Ill
LACV-Bunya
VEEV, EEE- Toga

JEV- Cx; Lg birds, pigs
VEEV- multiple; sm, lg mammals & birds
LACV- Ae, sm mammal
TBE, Louping Ill- Ixodes, sm mammal


*JEV- significant swine repro pathogen
*TBE- Central EU & Asia (distinct strains)
LISpain & British Isles - dz in humans, sheep, + horses
*Highland Jvirus closely related to EEE = SE USA

*Cx tarsalis, pipens feed on hu when no bird hosts avaialble

California group (ie. LACV) - encephalitis in humans & chipmunks: Aedes triceriatus "Eastern tree hold mosquito"

JEV- encephalitis in humans & horses - "arthropod virus of people"; mosquitoes are very efficient varriers
Term
Other zoonotic vector-brone viruses
Definition
DEN (flavi)- Ae aegypti, humans (other mammals) - fever, hemorrhage, shock (human)
CHIK (toga)- Ae, humans/primates - severe arthritic symptoms (humans), dz in primates - FOREIGN
YFV (flavi): Ae, haemoagogeus, humans/primates - generalized hemorrhage, rare encephalitis (humans); dz in primates - FOREIGN
CO tick fever (reo)- D. andersoni, sm mammal - NO Dz
RVF (bunya)- Ae/multiple afterward, ruminants - generalized hemorrhage, hepatitis, retinitis, rare encephalitis (hu); hihg mortality in ruminants - FOREIGN

*DEN is MOST infective arthropod borne vector of humans: mosquito-man-mosquito (Af = mosq-monkey-mosq in rainforests) ); wide range of mammilian sp incl 5 bats ie. S America: Sylvatic cycle
one genus - Artivius (bat sp) - nests in high areas close to human habitation
Ae where DEN is endemic - becomes active when bat is resting -> PI? Carrier-state? Dry period?

CHCK- also mosq-man-mosq
Term
Non-vector-borne zoonotic viruses
Definition
,antaviruses (bunya)
ie. Sin nombre, aka 4 corners virus
- sm rodents (mice, rates): saliva/urine/feces; retains infectivity , geo distinct hantaviruses have own host
ie. SN virus/4 corners virus: Peromyscus maniculatus
ie. NY virus: Peromyscus leucopus
- generalized, *focus on lung (human)

Old world hantaviruses
sm rodents
Hantaan virus (Korea) - host Apodemus sp - generalized, hemorrhage, w/ *focus on kidneys (human)

LCM virus (arena)
sm rodents (mice, hamsters) - aysmptomatic, meningitis (humans); unthriftiness, type 3 (animals)

*Hantaviruses (new & old world) outbreaks assoc w/ environmental conditions favoring large increases in rodent populations

Monkey B virus (herpes)
Macaques: bite/contact w/ open wounds ie. scratches, sores - ascending paralysisn, encephalitis (humans); vesicular lesions (animals)
Term
Criteria for vector competency
Definition
1. the vector must have access to feed and feed on hosts that support virus replication at levels that are infective for the vector
2. must be able to transmit the virus in quantities that will infect animals on which it feeds
Term
WNV viremia
Definition
~5% IR = 10^4 Cx; 10^5.5 Ae (~diff of 1.5 logs)

*NOTE: VEE = Horse is AMPLIFYING Reservoir host
WNV, WEE, EEE- horse is DEAD-END host
Term
General paradigms for maintenance and transmission
Definition
Mosquito-bird-mosquito: commonly assoc w/ viruses vectored by Cx -
ie. WNV, JE, SLE

Mosquito-mammal-mosquito: commoly assoc w/ viruses vectored by Ae
ie. YFV, DEG, - assoc w/ hemorrhagic dz
ie. LCV (tree hole mosquitoes) assoc w/ encephalitis

Tick-mammal-tick
ie. Tick-borne encephalitis virus (Central Eurpoean, Far Eastern viruses), Louping Ill
Term
WEE paradigm
Definition
generally occurs west of the MS River (closely related w/ Highlands J virus in E US)
Pirnciple epidemic vector is Cx tarsalis birds are the 1o host but there is a shift in feeding pattern from bird to mammal in late summer/early fall - exposure ends w/ first killing frost
overwintering (interepidemic survival) probably mosquito

some Ae spp can serve as BRIDGE VECORS in traansmission to humans & horses
Term
EEE paradigm
Definition
Ae sollicitans, vexons, Coquiiettida perturbans

occurs along Atlantic & Gulf coasts & Upper midwest along MS River
(also Cliseta melanura)
OW probably mosquito, migratory bids?

Larger bids ie. Emu, pheasant, others
Term
WNV paradigm
Definition
Maintenance/amplifying vectors (Cx) ->
Bird-mosquito-bird (enzootic, epizootic)
Rabbits, squirrels, chipmunks ->
Bridge vectors: Cx, Ae
-b> Dead end hosts: humans, horses, other mammals

*Crows & robbins serve as 1o amplifying host, OW in mosquito, possibly continuous in infection in birds

WNV is PI in HAMSTERS!!!
Term
LAC paradigm
Definition
Sm mammal reservoir -> Ae triseriatus (ie. eastern tree hole mosquito)-> Human = DEAD-END host (most severe in children

*breeds in tree holes, tire dumps, containers
Term
VEE
Definition
epidemic forms not in US but periodically emerge in South America & move N to US border as in early 1970s
-6 major variants: I, II, III, IV, V, VI
subtype I is divideded into 6 variants: endemic ID, IE, IF
epidemic IAB, C variants arise from mutations of endemic variants
Subtype II is endemic in Fl everglades

Killed vaxx
Term
YFV paradigm
Definition
Sylvatic cycle maintained in South America by Haemagogus sp in canopy; also ticks in dry season; Dz in NW Monkeys


Urban cycle: Ae aegypti has adapted to hu environment although it can be found in forested areas. Ae aegypti is also primary vector for DENG (Amyplifying!)
Term
TBE paradigm
Definition
TBE viruses occur in Central Eu, Asia

(Ixodes persulcotus, rincinus)
Louping Ill in UK, Ireland has similar cycle in sheep

Virus overwinters in tick
Term
RFV paradigm
Definition
1. Wet Season: virus infected flood water- Ae sp
2. Dry season: rains begin
3. Amplification -> HIGH VIREMIA
then Cx, other Ae, sp. etc involved
Term
Surveillance and control
Definition
Mosquitos: NJ light traps (abundance)
CDC light traps, oviposition traps: mosquitoes separated by sex, sp; females pooled in groups of ~50 and tested for viruses using ELISA Af capture &/or RT PCR, VI using suckling mice or cell mice or cell culture
Chicken sentinels - bled wkly assayed for Ab (ie. IgM for WNV, SLE)
Other - WNV & dead bird collection

Mosquito abundace/prevalence data to local health authorities (moquito control-insecticides, larvacides, elimination of breeding sites)
Term
Clinical presentation of WEE< EE, WNV in horses, Dx, Control
Definition
IP ~2-10 d
symtpoms: in-coordination, circling, sawhorse stance, head pressing, pharyngeal & esophageal paralysis, photophobia/blindness, hyperestheisia, stupor, coma, recumbance & opisthotonus
druation of symptoms ~4-9 d
some rule-outs: EHV1, rabies, equine protozoal myeloencephalitis (PM)

Dx & control:
Antemortem: virus specific IgM ie. WNV in serum, rising IgG titer
VI not effecitnt for WEE, WNV, EEE as viremia is generally absent by time noticed
RT-PCR of CSF possible: PCR of nasal swab can be used to rule out equine herpesvirus; PCR of saliva for rabies but virus not always present (hazardous procedure)

Postmortem: VI, RT-PCR brain tissue

Control: killed (WEE, EEE), vectored, plasmid vaxx (WNV)
Notes: EEE virus will infect & kill emus, pheasants, turkeys, and other lg birds. EEE can be transmitted by *pecking. Small passerifrmes are 1o hosts & dont die.
WNV will also cause fatal infection in domestic geese.
Term
VEE paradigm
Definition
Epi cycle: IAB, *IC - many mosquitoes - mosquitoes represent opportunistic, mammalophilic, ornithophilic spp-> Lg mammals & birds

Enzootic cycle: ID, IE, IF - Cx (melanoconin) spp -> sm mammals

VEE mutations in the 5' NTR & E genes

*IC evolves from ID
Term
VEE in the horse
Definition
VEE is similar to the other equine encephalitis viruses EXCEPT:
- viremia can reach 10^9 PFU/ml ie. horse serves as an AMPLIFYING host
- virus recovrered from nasal washing, eye washings, urine ie. contact infection is a possibility as virus can access CNS via olfactor nerve
- multiple organ systems infected
CF ~50-80%!
Epidemic forms of virus not currently US but potential exists

Killed vaxx available
Term
Classification: Togaviridae
Definition
alphavirus (~40 viruses transmitted 1o by mosquitoes) - at least 7 Ag complexes
WEE, EEE, VEE complexes > EEE complex (EEE & Highlands J virus)
Fish viruses: salmonid pancrease dz virus
sleeping dz virus of trout

Rubivirus (German measels virus)
Term
Classification: Flaviviridae
Definition
Flavivirus (~70 viruses transmitted by mosquitoes & ticks: mosquito-borne Ag groups
-YFV, DEN, JEV (JE group (JE, WN, SLE viruses)
-tick-borne Ag groups (mammalian & seabrid groups)

Pestivirus (BVD, CSFV, BDV) - not vectored

Hepacivirus (Hep CV) - not vectoreed
Term
Classificaiton: Bunyaviridae
Definition
Orthobunyavirus - >150 viruses distrubted among 18 antigenic groups - most are mosquito vectored, some by ticks & culicoiddes
- important groups/viruses: California group (LACV), Bunyawera group (Cache Valley virus), Simbu group (Akabane virus))

Phlebovirus: RFV
Nairovirus (NSD, CCHF0) - ticks

Hantavirus: not vectoreed by arthropods
Term
Equine herpesviruses
Definition
rapid replication/lysis; latency assoc w/ sensory ganglia, lymphoid tissue)
-EHV1 (Eq abortion virus)
EHV4 (eq rhinopneumonitis)
EHV3 (Eq coital exantehma)
-EHV 6,8,9 (latter very similar to neurological strians EHV1)

Gammaherpesviruses (slow replication; narrow host range; lymphotrophic)
- EHV2,5,7
2-assoc w/ mononucleosis-like syndrome of foals
5- progressive pulmonary fibrosis syndrome
7- encephalitis of donkeys

EHV1, VEE + URT
Others- NOT URT (WNV, EHV4, EEE, WEE, etc)
Term
EHV1
Definition
abortion usually late term w/ fetus in relatively good condition; "ABORTION STORMS" occur in susceptible populations w/ rapid spread of virus via contact w/ contaminated conceptus; perinatal mortality:
focal necrosis in liver, interstitial pneumoni, etc

Respiratory dz
encephalomyeltiits (assoc w/ specific strains): vasculitits of cerebral vessels, thrombosis, neurla dgeneraation
Term
EHV4
Definition
profuse serous nasal discharge becoming mucopurulent-
common in foals as maternal Ab declines, recrudescence common throughout life
rarely assoc w/ abortion
Term
EHV3
Definition
self-limiting vesicular, ulcerative lesions of genital mucosa and surrounding skin, occasionally on lips, muzzle, teats
Term
Dx & control of Eequine HV
Definition
common rule-outs; vector-brone encephalitis viruses , rabies, EPM
VI, PCR, SEroligcal: PCR of nasal swab is effective
Mmgt: isolation; infection control; consider latency
Term
EAV
Definition
Usually asymptomatic, abortion w/in month of infection (strain dependent), fetus commonly autolyzed, abortion storms occur

Others-
commonly presents as URTI ie. conjuncivitis, rhinitis, nasal discharge: foals sometimes develop fatal bronchointerstitial pneumonia
*edema: palpebral, ventral, hind leg; assoc w/ vascular lesions: sm segments of intestinal necrosis in young
pleural & pericardial effusions

PI common in stallions**, lasts mos-lifetime iel. STALLION = RESERVOIR: PI NOT recognized in mares, foals prior to puberty & geldings - ie. toestosterone dependent: vaxx of foals prior to puberty inhibits PI!!!

Transmission via aerosols, fomites, contact; and veneral via PI stallion/AI

Dx, control: VI, PCR, serology

Live & killed vaxx
Management
Term
EIA
Definition
A/Maiami/2/63 (H3N8); Eq type2, most important worldwide (this is the subtype w/ mutations now in North American dogs!):
-divergence of H3N8 into Eurasian & North American lineages ie. FL, KY - Ag drift
- URT dz more explosize & rapidly spreading vs. EH4 & EHV1

mortality rare - but in 1989 Mongolian/China eq H3N8 outbreak; morbitditiy:mortality::80:20%: virus evolved from Avian H3N8, 6 or 8 segments of Avian origin*

control via vass:
i. Cold adaptive
ii. Canarypox vectored vaxx

Note: A/Prague/1/56(H7N7); eq type 1 has not been isolated for yrs!
Term
ERAV (Eq Rhinitis A virus)
Definition
member of Apthous genus (~FMD); present as fever, nasal discharge, pharyngitis (persistent cough 2-3 wks), lymphadentitis, bornchitis (~EHV & EAV):
virus shed via nasal secretions & ruine
transmitted by aerosol & close contact

Old & New world camelids susceptible: abortion, wasting dz in *New world camelids: virus infection of islet cells of pancrease (note: some strains of coxsackie virus also infect/kill islet cells)

Dx & control
-dz is *self-limiting
information lacking on risk to camelids housed in close proximiting to infected horses
Term
EIA
Definition
lentivirus causing acute to chronic infectious dz of horses (donkeys, mules) characterized by recurrent bouds of: fever, anemia, thrombocytopenia, icterus, edema: anemia not generally seen until recurrent episodes
GN may eventually occur (DTH3)
mortality rates can be >50%

Transmission iatrogenic or mechanical: biting insects ie. Stomoxys spp, Culicoides spp & other biting flies (esp -successful transmissino 1:7 attemps via Horse fly)

Control-
ID infected via COGGINS test or ELISA, can confirm by PCR
Quarantine new stock 45 d & retest
stable infected horses >200 yrds from uninfected
no vaxx available to US!: role of Neutralizing Ab unclear!~
Term
VSV
Definition
Rhabdovirus; causes self-limiting vesicular dz of horses, cattle, swine, lesions ~ fmd
mechanical transmission by fomites & biting insects (outbreak probably initiated via biological vector)
- Lutzomyia (sandflies), Simulidae (black flies), culicoides (midges) can serve as bioological vectors
-VSV retains infectivity few ds moist, cool conditions w/ organic material ie. milking machines
zoonotic IV-like illness, vesicular lesions in mouth reported

*Disappears after Killing frost!!!
No vaxx!
Term
Eq papilloma virus
Definition
Eq pappilomaviruses (warts) & sarcoids (strong evidence due to bov papillomavirus 1,2)
Term
Hendra virus
Definition
emerged 1994 Aus, member of Heniphavirus of Paramyxoviridiae
-zoonotic (h*HIGH human mortality)
-FRUIT BATS (megachroptera) are natural reservoir
-ARS (clear to sero-sangiuinous), edema, cyanosis, CNS involved (head pressing, ataxia), death ie. HIGH MORTALITY
*virus SHED PRIO to clinical signs!!!


BSL4!!!!!!!!!!!
Term
AHS
Definition
FAD: an orbivurs of the Reoviridiae: severe systemic dz: pulmonary & cardiac forms, high mortality
Affects Eq, mules, donkeys, zebras (dogs that eat carcasses)

vectored 1o by Culicoides

Vaxx available (9 known serotypes)


(pullmonary-> foaming nasal discharge; Cardiac -> severe swelling/edema & sero-sanguinous discharge from mucosa outles/eyes, etc
Term
Herpesviridae
Definition
envelopd glycoprogies: gA-gE
biological characteristics: vesicular lesions of mucosa & skin; gerneralized infection w/ focal necrotic lesions common; also affect RT, Repro, CNS
latency w/ intermittent shedding (some *Beta can be continuously shed)
genreally m ore severe in young v. old, less severe in natrual nost
INIB
cool, moist environment promotes survival

6 subfamilies : alpha, beta (cytomegalo viruses), gamma (lymphotrophic), alloherpes (channel catfish virus), malacoherpes (oysters)
Term
Arteriviridae
Definition
+sslinear RNA, enveloped: major env proteins: E, M, GP5 (alpha recep)

Biological characteristics:
-asymptomatic PI in natural hosts
sme arteriviruses: EAV, PRRSV, *SHF (Simian hemorrhagic fever) virus

Note; reston virginia ebola (filoviridae) outbreak was originally through tot be SHF virus - reston originated in the phillipines where it has since affected pigs, humans (no deaths as is rule w/ Af isolates). Reston virus causes repro failure & severe Resp dz in pigs.
FOREGIN
Term
orthomyxoviridae
Definition
enveloped, helical, segmented -ssRNA

Biological characteristics of type A IV:
high rate of mutation (Ag drift)
genetic reassortment (Ag shift)

3 genera:
IV (8 segments): evolved into 5 lineages ie. gulls, swine, human, old horse & new horse (virus evolvedvirus evolved from avian virus)
-3 types: A,B,C based on internal proteins: subtypes of A based on H & N

Thogotovirus (tick transmitted)
Isavirus (infectious salmon anemia virus)
Term
Picornaviridae
Definition
sm naked +ssRNA - very stable outside host

6 established genera
aphthovirus: FMD not in horse, ERAV
Enterovirus: swine vesicular dz (FAD), coxsackie viruses ie. handfoot-and-mouth dz, human poliovirus, human & bovine rhinoviruses
Cardiovirus: encephalomyocarditis virus
Teschovirus: porcine TV1 (formerly porcine entero virus1), aka pig polio (Teschen dz, Talfan dz in Eu)
Hepatovirus: Hep AV
Term
Retroviridae
Definition
enveloped, DIPLOID RNA ie. 2+ RNA strands covalently linked; major env protein s SU

Biological characteristics
reverse transcriptase (note revTET has -both R & D pol activity)
-PI (latent)

Genera:
alpha, beta, gamma, omega, epsilon (oncoviruses)
Lentivrus (EIA, HIV, FIV, CAEV)
Spumaretrovirinae (significance of members unknown)
Term
Rhabdoviridae
Definition
-ssRNA, 1 envelope protein = G

Genera
Lyssavirus (rabies)
vesiculovirus (VSV): 2 serotypes in US
i. VSV-NJ (New jersey)- iso in 1926 from cattle, most common
ii. VSV-IN (indianta) isolated 1925 from cattle, last isolated 19656 - uncommon: variants w/in serotypes

Ephemoerovirus (bovine ephermeral fever FAD, arthropod transmission)
Novirhabdovirus (infectious hematopoetic necrosis virus of salmoids, viral hemorrhagic septicemia virus, snakehead virus)
Term
Papilomaviridae
Definition
naked, circular dsDNA
- CANNOT grow in cell cultre
-typed by nucleotide sequences (PCR) & host specificity

Warts in all spe, some can lead to maligancy ie. bov 4, rabbit & hu types

Eq sarcoids
-histo: ~ fibrosarc
-bov1,2 are probable cause: exerimental inj results in eq sarcoid but unlike natraully occuring sarcoids they regress spontaneously*; DNA of the bov viruses have been detected in eq sarcoids
Term
Paramyxoviridae
Definition
pleomorphic, lg-med size, env, *helical, -ssRNA: env contains 2 glcoproteins: HN, H, G depending on virus; F (fusion protein)= virulence actor

2 subfamilies-
Pneumovirinae: BRSV (pneumovirus), Turkey rhinotracheitis (metapneumovirus): severe resp dz

paramyxocirinae (5 genera)
respirovirus: bov PI3, Sendai PI1
Avulavirus: : NDV - lentogenic, mesogenic, velgenic (FAD)
Rubulavirus: canine PI5 (formerly PI2), Simian PI5 (~canine PI5) hu PI2, por rubula virus (FAD), aka blue eye (Mexico), Human Mumps virus
Morbilivirus: CDV, Rinderpest (now eradicated), Measela (the medipest group), Peste de petitie ruminants, morbilliviruses of seals/dolphins/porpoises
Heniavirus: Hendra, aka eq morbillivirus, Nipah virus of pigs (BSL4 agents) both FAD
Term
Reoviridae
Definition
med, naked, 2-3 capsid layers, *SEGMENTED ds RNA, "wheel" appearance

5 genera
biological characteristics depend on genus:

arthropod-borne: Orbivirus: BTV, epizootic hemorrhagic dz of deer (EHD), AHS: Coltivirus Co tick fever virus, a zoonotic

Non-arthropod-borne:
Rotavirus (enteritis, mammalian sp)
Orthoreovirus: reoviruses of rodents; avian orthoreoviruses; tenosynovitis, arthritis most common effects but others incl resp, GI, liver, runting etc.
Term
Adenoviridae
Definition
Lg-med naked nucleocapsid, dsDNA - unique penton fibers on vertices w/ HA activity

gerna incl:
Mastadenovirus: CAV1,2; Eq adenovirus- resp dz in SCID foals
Aviadenovirus: Qual bronchitits virus
Atadenovirus:: odocoileus adenovirus 1 (fata hemorrhagic generalized dz, west coast); egg drop syndrome (egg defects ~ IBV), adenoviruses of reptiles)
Siadenovirus: hemorrhagic enteritis of turkeys
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