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Virology - retrovirus
Viruses
123
Veterinary Medicine
Undergraduate 3
06/01/2012

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Term
EM of retrovirus =
Definition
3 ring structure
Term
capsid of retrovirus =
Definition
icosahedral (outer) and helical (inner)
Term
genome of retrovirus =
Definition
2 identical copies of +ssRNA ONLY VIRUS WITH DIPLOID GENOME +ssRNA's have a cap, poly A tail and 2 untranslated regions and repeat seq at each end and a gag, pol and ENV region
Term
rotavirus polymerases make...
Definition
...DNA
Term
unusual things about rotavirus =
Definition
1. only virus with diploid genome
2. only RNA virus that goes into vell and doesnt immediately start replicating
3. only viral RNA to be synth and replicate dby host enzymes
Term
viral reverse transcriptase makes...
Definition
...dsDNA from +ssRNA This DNA is called cDNA (complimentary DNA)
Term
viral reverse transcriptase has what polymease activity?
Definition
RNA dependant DNA pol activity and DNA dependent DNA pol activity
Term
where does viral reverse transcriptase bind to viral +ssRNA?
Definition
the middle and repeated regions of +ssRNA bind = big circle of +ssRNA
Term
can reverse transcriptase of +ssRNA occur in vitro?
Definition
yes
Term
does retrovirus nucleocapsid contain everything it needs for reverse transcriptase of +ssRNA?
Definition
nearly
Term
reverse transcriptase of +ssRNA into ds cDNA occurs in...
Definition
...viral capsid = no IFN response/induction
Term
what happens to cDNA of rotavirus?
Definition
several copies of cDNA are intergrated into host genome at random loci by viral integrase enzyme

all this time virus is invisible to immune system!!

NOt really random as can only insert cDNA where host cell DNA is unwound (and therefore active)
Term
whats in rotavirus icosahedral nucelocapsid?
Definition
2 identical strands of +ssRNA
integrase
reverse transcriptase
protease
nucleoprotein (helical capsid containing +ssRNA)
Term
untranslated sequnecs at end of virus gene =
Definition
promoters (strong if need alot of that protein, weak if dont)
Term
once cDNA in host cell DNA get synth of cDNA into mRNA by...
Definition
...host cell mRNA pol = synth of new virus proteins and genome
Term
exit of rotavirus from cell =
Definition
budding from host cell surface
Term
viral oncogenes =
Definition
viral genes that promote tumour development
-DONT have introns
-expressed out of their normal cellular context
-under control of strong viral promoters
-have high freq of mutations (due to cutting and pasting by viral integrase)
-generated during reverse transcriptase of +ssRNA
Term
viral oncogenes cause:
Definition
1. promote virus growth
2. promotion of host cell growth genes = incr growth
Term
cys-acting =
Definition
strong viral promoters inserted close to cellular oncogenes may induce overexpression of the cellular oncogene
Term
5classes of retrovirus =
Definition
1. replication-competent
2. replication-defective rapidly transforming
3. replication-competent rapidly transforming
4. trans-acting
5. endogenous retrovirus (ERV)
Term
what class of retrovirus doesnt have pol gene?
Definition
replicative-defective
Term
rous sarcoma virus is what type of retrovirus?
Definition
replication-competent rapidly transforming
Term
promoter=
Definition
effects expression of genes
Term
transcription factor =
Definition
effects transcription of genes
Term
which class of retrovirus doesnt have any promoters?
Definition
ERV
Term
what can activate replication of ERV?
Definition
irradiation
mutagen
immune stimulus
other retroviruses nearby with promoters
Term
name a transacting retrovirus
Definition
bovine leukameia virus
Term
viral transcription factor genes =
Definition
tax and rex
Term
what limits replicating-competent rapidly transforming retrovirus?
Definition
its very big = constraint on virus = more likely to make mistakes and get mutations on replication
Term
what limits replicating-competent rapidly transforming retrovirus?
Definition
its very big = constraint on virus = more likely to make mistakes and get mutations on replication
Term
avian retrovirus =
Definition
alpha retrovirus
Term
all chickens have...
Definition
...ERV (rarely expressed, not pathogenic)
Term
avian leukosis virus =
Definition
exogenous virus
replication competent
no v-onc
cis-acting(slow forming)
cause dz sporadically in birds
Term
infection with avian retrovirus =
Definition
transient viraemia
immunity
leukaemia (rare)
Term
vertical transmission of retrovirus in poultry results in...
Definition
...immune tolearnt chicks
-chronic virameia
-leukaemia (common)
-spreads infection to rest of flock
Term
dz of avian retrovirus depends on...
Definition
...what cell type is infected (causes incr in this cell type/ growth)
Term
most common dz caused by retrovirus in birds =
Definition
B cell lymphoblastoma

occurs following insertion of virus close to c-myc oncogene, which encodes a cellular transcription factor
Term
latent ERV in chick =
Definition
healthy chick
no viraemia
no leukamia
chick may not be immunotolerant to virus as virus isnt expressing any genes
Term
retrovirus in cats =
Definition
FeLV
Term
infection of FeLV occurs in...
Definition
...high density cat populations via resp, groomiing or bites
Term
FeLV infection in adult cat =
Definition
immune response and celar infection
neutralising Abs stop spread
cytotoxic Tcells

cant get rid of cell with viralDNA integrated into genome though!!
Term
FeLV is what class of retrovirus?
Definition
replication-competent (no oncogene, cis-acting0
Term
infection of preg queen or newborn kittens =
Definition
50% of kittens = immune response and clear virus

50% of kittens = no immune response, persistant viral infection, immunotolerant = shed virus all the time and can develop tumours
Term
FOCMA =
Definition
Feline Oncovirus Cell Mb Ag

an oncovirus that can cause cancer
Term
FOCMA is an ENV gene product of what class of FeLV?
Definition
ERV
Term
lymphocytes ifected with virus containing FOCMA =
Definition
express FOCMA on cell surface
Term
infection of immune cats with FeLV =
Definition
self limitng as cat got Abs against viral Abs and FOCMA non-viraemic
Term
FeLV infection of immunotolerant cats =
Definition
perisitant infection with viraemia
no Abs against viral Ags or FOCMA
carriers

(thereofre cant detect FeLV by looking for Abs)
Term
3 antigenic types of FeLV are recognised based on their ENV glycoprotein. WHat are these?
Definition
FeLV A
FeLV B
FeLV C
Term
most common types of FeLV =
Definition
FeLV A
Term
what FeLV is present in all cases of FeLV>
Definition
FeLV A
Term
which FeLV is most readily transmitted?
Definition
FeLV A
Term
FeLV A binds to...
Definition
...thiamine transport protein 1 (THTR1)-commonly expressed on replicating cells
Term
most commonly FeLV A causes...
Definition
...lymphosarcomas (=30% of feline tumours)

-thymic
-multicentric
-alimentary
Term
what other dz can you get with FeLV A?
Definition
myeloproliferative dz - XS BM prolif
Term
FeLV B =
Definition
recombinant of FeLV A ENV genes with ENV genes of ERV = change R

new R = Pit1(or 2) phosphate transporter
Term
FeLV B can only be transmitted with...
Definition
...FeLV A and dies out after passage
Term
combined infectiond of FeLVA and FeLVB =
Definition
more rapid ds progression
Term
FeLVC arises from
Definition
FeLVA mutaion of ENV GP70 = change R = haem exporter
Term
FeLVC causes
Definition
rapid and fatal anaemia as attacks RBCs
Term
what FeLV is NOT transmitted?
Definition
FeLVC
Term
Dx of FeLV =
Definition
detection of virus Ag in blood or serum via ELISA test

(Abs no gd for detection of FeLV as can get immunotolerant cats)
Term
FeLV oncogene =
Definition
tyrosine phosphokinase
Term
how do fibrosarcomas in yound cats develop from FeLV?
Definition
FeLV oncogene fuses with gag protein and is inserted into cell mb = development of multicentric fibrosarcomas
Term
feline sarcoma virus is what class of retrovirus?
Definition
replication-defective rapidly transforming retrovirus
Term
feline sarcoma virus manages to survive and replicate due to...
Definition
...packaging/ infection along with FeLV A
Term
prevention of FeLV =
Definition
testing and removing infected cats from catteries to decr spreading, espec queens (due to vertical transmission)
Term
FeLV vacc?
Definition
1. cell culture derived glycoprotein 70, FOCMA AG (from FeLVA) 2. E. coli expressed subunit vacc - leucogen 3. recombinant canary pox virus (big genome so can manipulate alot so can put FeLV in genoma so poxvirus expresses gp70 = viral specific immune response :)) -canary poxvirus doesnt grow well in mammals :)
Term
beta retrovirus dz =
Definition
ovine pulmonary adenomatosis (Jaggsiekte)
Term
where is ovine pulmonary adenomatosis found in the world?
Definition
everywhere except australia
Term
ovine pulmonary adenomatosis causes...
Definition
...neoplastic transformation of type II alveolar cells and non-cliated bronchial epi cells
Term
do beta retrovirus have oncogenes?
Definition
no, cis-acting??
Term
ENV protein of beta retrovirus binds to...
Definition
...hyaluronidase 2
Term
hyaluronidase 2 =
Definition
enzyme on surface of many types of cells
Term
Jaggsiekte/btea retrovirus ENV protein acts as an......
Definition
... oncogene through binding to phosphatidylinositol 3-kinases (PI3), espec when in lung cells
Term
effected sheep AB RESPONSE TO beta retrovirus =
Definition
NO Ab response to ENV protein, as the presence of closely related ERV causes the sheep to be immunotolerant to the jaagsiekte virus
Term
ENV protiens from ERV =
Definition
not usually expressed and dont bind to PI3 = lack transforming properties
Term
why is there tolerance to ERV and thereofe exogenous jaagsiekte retrovirus as well?
Definition
ERV ENV protein is expressed in placenta where it may have an imp function in development of multinucleated trophoblast cells essential fro implantation = essentail for sheep breeding! Explaining the development of tolerance to ERV and thereofre jaagsiekte virus too
Term
jaagsiekte spread by...
Definition
...resp route
Term
following of intro of jaagsiekte virus into herd dz incidence can be as high as...
Definition
20%
Term
how many sheep become affecte by beta retrovirus in endemic flock?
Definition
1-5%
Term
beta retrovirus is v common in what breed of sheep?
Definition
scottish black face
Term
clinical signs of jaagsiekte =
Definition
breathlessness
lung sounds
large amount of pulm fluid (wheelbarrow test)
Term
adenocarcinomas/adenomas =
Definition
secrete large amounts of surfactant
metastisize to LNS
Term
test for proviral DNA of beta retrovirus =
Definition
PCR - amplifies LTR (long tandem repeat seq = gd as wont get false + result when just got ERV as ERV has no repeat seq/promoter regions)
Term
in beta retrovirus infected flock many sheep have virus in peripheral blood lymphocytes than have lung lesions and dont get tumours, despite lack of Ab response. Why is this?
Definition
expression of mutant gag proteins from some ERVs disrupts assmebly and exit of mature wild type/virulent virus and thereofre limits spread in lungs and prevents tumour development
Term
name a lentivirus
Definition

FIV

maedi/visna

carpine arthritis

equine infectious anaemia

Term
prevelance of FIV =
Definition
common and widespread
Term
how many healthy cats are + for FIV Abs?
Definition
1% of healthy cats
Term
how many sick cats are + for FIV Abs?
Definition
30%
Term
infection of FIV is
Definition
lifelong
Term
FIV is shed in...
Definition
...saliva and blood
Term
infection of FIv can occur by...
Definition
...fighting
transplacental infection
at parturtion if mum viraemic
Term
FIV ENV binds to...
Definition
...CD134 and CXCR4
Term
FIV infects
Definition
activated CD4+ Thelper cells
Term
acute phase I of FIV (2months) =
Definition
viraemia
infection spreads to more CD4+Tcells
replication
fever
malaise
lymphadenopathy (dz of LNs)
Term
initial immune response to FIV =
Definition
Ab production and cytotoxic CD8+Tcells = reduce no of infected CD4+Tcells and apparent clinical recovery

BUT CD4+Tcells containing provirus (incorporated into host cell genome) cant be eliminated :(
Term
Phase II of FIV (may last several yrs)
Definition
mutation of virus epitopes allows it to escape CD8+Tcells
gradual derc in CD4+Tcells
recurrent cycles of expansion, immun elimination, mitation and expansion again.....
Term
decr CD4+tcells =
Definition
impaired immune function:
-decr IL2
-decr Ab
-decr blastogenesis
-decr CMIR

=immunodeficiency and predisposition to opportunistic pathogens
Term
Phase III of FIV infection =
Definition
-onset of symptoms due to immunosupression associated with opportunistic infections
-high freq fever, gingivitis and mouth ulcers
-strong association with FeLV and Bcell lymphomas
-neuro signs if astrocytes and microglial cell infection predominates (rare)
Term
Dx of FIV =
Definition
detectionof Abs to virus
Term
tx of FIV =
Definition
AZT = inhibit Reverse transcriptase

(partially effective)
Term
FIV vacc?
Definition
no effective vacc :( as virus persists in the presence of Ab and cytotoxic resposne
Term
name 4 lentiviruses
Definition

maedi/visna caprine arthritis/encephalitis equine infectious anaemia/swamp fever

FIV

Term
maedi infects
Definition
monocytes and monocyte precursors
Term
infected monocyte activation =
Definition
activate virus replication
Term
onset of dz with maedi =
Definition
late onset

lifelong infection
Term
symptoms of maedi
Definition
-chronic inflam/fibrosis induced by infected monocytes
-breathlessness
-consolidation of lungs
-enlarged bronchial LNs
-hyperplasia of alveoalar septae
-monocyte infiltartionof alveolar septae
Term
visna infection =
Definition
chronic demyelinating encephalitis with moncyte infection

rare
Term
why does maedi/visna persist in presence of Ab and CMIR?
Definition
poss due to constant mutation
Term
transmission of maedi/visna =
Definition
-to lambs in mums colostrum
-aerosol (from symptomatic sheep)
-biting insects = mechanical vectors
Term
control of maedi/visna =
Definition
eradication of...
...symptomatic sheep
...sero+ sheep
...PCR + sheep
Term
similar virus to maedi/visna seen in goats =
Definition
caprine arthritis/encephalitis
Term
caprine arthritis/encephalitis causes
Definition
proliferative synovitis lesions with lymphocyte, plasma cell and moncyte infiltration
Term
caprine arthritis/encephalitis spread in...
Definition
...colostrum and milk
Term
kids infected with caprine arthritis/encephalitis develop...
Definition
...neuro signs
Term
what lentivirus is a notifiable dz in UK?
Definition
equine infectious anamia/swamp fever
Term
equine infectious anamia infects
Definition
macro and mono
Term
equine infectious anamia signs =
Definition
-freq assymptomatic, therefore hard to eradicate

-virulent strains of equine infectious anamia cause:
acute viraemia
anaemia
thrombocytopaenia
Term
pathology of equine infectious anamia infection -
Definition
cyclical. virus escapes immunity and causes dz, then immunity gets on top, then escapes immunity again etc......
Term
prognosis of equine infectious anamia =
Definition
partial recovery with time
Term
coggins test =
Definition
looking for Abs in blood to test for equine infectious anamia
Term
vacc for equine infectious anamia?
Definition
chinese attenuated vacc: to get over 1st phase, but then persistently infected

only china uses this vacc as other countries trying to eradictae equine infectious anamia
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