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MicroQs Assessment 7
UTHSC College of Medicine Micro Qs Assessment 7
231
Microbiology
Professional
10/04/2011

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Cards

Term
Into which family and genus does the measles virus fall into?
Definition
Considered a "new" virus of human, it falls in the morbillivirus genus of Paramyxoviridae family.
Term
How is measles differentiated from other paramyxoviruses? (others we've studied= RSV, hPIV, Metapneumo)
Definition
lacks neuraminidase activity (has H protein rather than HN) and forms intracellular inclusion bodies
Term
Is measles + or - strand?
Definition
NEGATIVE
Term
Is mumps + or - strand?
Definition
NEGATIVE
Term
Is rubella + or - strand?
Definition
POSITIVE
Term
How is measles the same as other paramyxoviruses?
Definition
same replication strategy and similar to all non-segmented, negative strand RNA viruses
Term
How is measles different from other paramyxoviridae?
Definition
Receptor usage: primary MV receptors are CD46 and SLAM; measles has H protein; forms intracellular inclusion bodies (dstinctive feature of cytopathology)
Term
What is the required population size of measles?
Definition
> 100,000; reservoir of susceptible individuals
Term
What was the avenue of transmission (historically) for measles?
Definition
trade between China, Europe, India, Middle East (massive epidemics in 2nd, 3rd, 4th centuries)
Term
What are the 3 steps of entry and replication of measles virus?
Definition
MV binds to receptor (CD46; SLAM/CDw150); binding activates F protein which causes membrane fusion (virus entry); replication and virus assembly is simlar to that of other negative strand RNA viruses
Term
What receptor does the vaccine strain of Measles virus use?
Definition
CD46
Term
What does SLAM stand for (measles virus receptor)?
Definition
WT MV= SLAM= signaling lympohcyte activation molecule
Term
What is the pathogenesis of measles?
Definition
highly contagious; typically a childhood infection; spread via respiratory route; has a latent period and a prodrome that is followed by the characteristic maculopapular rash
Term
How long is the latent period in measles?
Definition
10-14 days
Term
How long is the prodrome period of measles and what occurs during that period?
Definition
2-3 days of fever, cough, conjunctivities (followed by rash)
Term
What is the characteristic feature of measles?
Definition
appearance of maculopapular rash after prodrome symptoms
Term
What is mortality mainly due to in measles?
Definition
bacterial pneumonia
Term
What does the measles rash coincide with (immunologically)?
Definition
T cell response and virus clearance (CD4 response peaks around 12 days, CD8 response around 15 days, IgM around 16 days; IgG climbs starting around 19 days)- see chart in prestudy notes
Term
What is the clinical case definition of measles?
Definition
Generalized rash lasting > 3 days; temperature >38.3°C (101°F); cough and/or rhinorrhea and/or conjunctivitis
Term
Should you report measles-like symptoms to MMWR/state health dept?
Definition
If patient with symptoms is epidemiologically linked ot another confirmed/probably case of measles, then YES
Term
What occurs during the early stage of measles infection?
Definition
Initially: virus replication restricted to tracheal and bronchial epithelium/ After 2-4 days: infection spreads to lymph nodes
Term
What does measles replication in lymphoid tissue result in?
Definition
appearance of lymphoid or reticuloendothelial giant cells--> AKA Warthin-Finkeldey cells
Term
What are Warthin-Finkeldey cells?
Definition
lymphoid/reticuloendothelial giant cells found in early stages of measles
Term
What does amplification in lymph nodes in measles lead to?
Definition
Viremia and infection of other tissues and organs
Term
When do symptoms of measles occur?
Definition
soon after onset of viremia
Term
When is patient infectious in measles?
Definition
1-2 days before symptoms occur (10-20 days following exposure)
Term
What are the symptoms of measles?
Definition
maculopapular (or morbilliform) rash and Koplik spots
Term
What is the measles rash a result of?
Definition
infection of dermal endothelial cells followed by spread to overlying epidermis
Term
What are Koplik's spots?
Definition
small red spots (typical to Measles) with blue-white centers on inside of upper lip and cheek; often seen BEFORE the rash
Term
What are some measles virus complications?
Definition
immune suppression during measles virus infection; postinfectious encephalomyelitis (PIE); measles inclusion body encephalitis (MIBE); and subacute sclerosing panencephalitis (SSPE)
Term
What happens during immune suppression in measles virus infx?
Definition
suppression of delayed type hypersensitivity skin test responses; antibody and cellular immune responses to new antigens are also impaired (see graphs in p2 of notes- it looks like reactions return as symptoms subside)
Term
How long does immune suppression last in measles?
Definition
DTH is suppressed from before onset of rash and continues for approx 1 month; Ab and cellular immune response to new Ag also impaired
Term
Why is there an impairment of Ab production and cellular immune response in measles?
Definition
infection of monocytes and other immune effector cells (probably) are the primary cause of measles virus-induced immune suppression
Term
What occurs in PIE?
Definition
aka autoimmune demyelinating disease; associated with an immune response to myelin basic protein; mechanism for induction is not known
Term
What occurs with MIBE and SSPE?
Definition
result from establishment of persistent infections in the brain; mechanism of entry to CNS is not understood
Term
What is the timeline for the measles virus complications?
Definition
PIE may overlap somewhat with the rash, peaks at 21 days, and subsides after a month; MIBE begins around 1 month, peaks around 4-5 months, and subsides by 9 months; SSPE begins around 3 years and subsides around 12 years
Term
Inclusion body encephalitis: host? Typical age? MV in brain? Incidence? Pathology? Time course?
Definition
Immunosuppressed host, any age, MV in brain, incidence unknown, inclusion bodies, progressive over months
Term
Postinfectious ecephalomyelitis: host? Typical age? MV in brain? Incidence? Pathology? Time course?
Definition
normal host, >2 years, no MV in brain, 1:1000 cases, inflammation and demyelination, monophasic over weeks
Term
Subacute sclerosing panencephalitis: host? Typical age? MV in brain? Incidence? Pathlogy? Time course?
Definition
normal host, < 2 years, MV in brain, 1:106 cases, inclusion bodies and inflammation, progressive over years
Term
How do we prevent measles?
Definition
currently use a live-attenuated measles virus vaccine; provides "life-long" protection
Term
When are children vaccinated against measles?
Definition
use trivalent MMR at 12-15 months (can be earlier but not before 6 months); 2nd dose at 4-6 years; given SubQ
Term
What is an important characteristic of measles and mumps viruses (in terms of immunity)?
Definition
antigenically stable monotypic viruses; immune for life once recovered from measles (immune against all strains b/c neutralizing antibody to one strain will protect an individual against all currently circulating strains)
Term
Why a recent resurgence in measles virus?
Definition
dramatic increase from 1989-1991 and additonally in 2001, 2008, and 2011; 2001 and 2008 resurgence due to low vaccine coverage (parents refusing to vaccinate…he does not give explanations for resurgences in other years)
Term
MMR vaccine and autism????
Definition
no scientific evidence of MMR vaccine causing vaccine!!!
Term
How are different measles strains defined?
Definition
amino acid differences in H or HN proteins
Term
Why are measles an ideal candidate for eradication through immunization (like mumps)?
Definition
only one serotype; most cases are clinically identifable; no animal reservoir; "herd immunity" is required (eradication=at least 98% of population is immune)
Term
What have been the resutls of the international vacciation campaign?
Definition
initiated in 2001 and seen global deaths from measles drop 50%
Term
Why should people who were vaccinated against MMR in 1963 and 1967 get revaccinated?
Definition
their inactivated vaccine was not effective; they should be revaccinated with live, attenuated dose
Term
What are factors limiting vaccination for measles? Aka what are the contraindications for vaccination?
Definition
anyone who has had a life-threatening allergic rxn to gelatin or neomycin; those who are moderately or severely ill at time of vaccination (wait until recovered); pregnant women (do not get pregnant until at least 4 weeks after vaccination); anyone on immunosuppressive drugs or immunocompromised for other reasons
Term
What family/genus is mumps a member of?
Definition
rubulavirus genus of Paramyxoviridae family
Term
Is mumps as infectious as measles?
Definition
no
Term
What is the pathogenesis of mumps?
Definition
initially affects nasal mucosa and upper respiratory tract epithelium, incubates approx 18 days, spreads to draining lymph nodes, virus sheds in saliva for approx 6 days before onset of clinical disease
Term
What are the first clinical signs of mumps?
Definition
infection of parotid gland- 95% of all symptomatic cases
Term
What do mumps complications include?
Definition
CNS involvement: aseptic meningitis , deafness- approx 1/2 of mumps infections result in some virus replication in CNS
Term
How long does it take for aseptic meningitis caused by mumps to resolve?
Definition
3-10 days
Term
How is deafness caused by mumps?
Definition
infection of cochlea (1/20,000)
Term
What are some other mumps complications?
Definition
symptomatic gonadal involvement ("orchitis") in post-pubertal men; correlation of mumps and type I insulin-dependent diabetes; myocardial invasion; high incidence of featal wastage leading to spontaneous abortion if contracted during 1st trimester of pregnancy
Term
How do we prevent mumps?
Definition
live-attenuated vaccine: safe, effective, few adverse effects
Term
What type of virus is Rubella? (genus, family, RNA or DNA, +/- strand, small or big, enveloped or not, segmented or not)
Definition
Togaviridae; genus Rubivirus; RNA, + strand, small, enveloped, nonsegmented
Term
What are alphaviruses?
Definition
A genus of Togaviridae; Western equite encephalitis, EEE, VEE viruses; all are arthropod-borned viruses
Term
What are rubiviruses?
Definition
Rubella is the only member of this genus that is part of Togaviridae; distiguished from alphaviruses by its limited host range (humans)
Term
In the rubella replication cycle, how does the virus enter the host?
Definition
enters by receptor-mediated endocytosis and viral envelope fuses with endosomal membrane in a pH-dependent manner
Term
In the rubella replication cycle , how is the viral polymerase translated?
Definition
genome serves as mRNA for translation of viral polymerase; polymerase synthesizes a negative strand antigenome (replicative intermediate)
Term
What is the negative sense antigenome use for (in rubella virus)?
Definition
used as a template to synthesize subgenomic mRNA encoding viral capsid and envelope proteins (as polyprotein) AND more full-length, positive strand genomic RNA (progeny)
Term
How is rubella transmitted?
Definition
primarily by aerosoles
Term
Where does rubella virus replicate?
Definition
initially in mucosa of upper respiratory tract and nasopharyngeal lymph nodes
Term
What are the 4 things to know about rubella virus replication? (from picture in slideset)
Definition
enters cell by receptor-mediated endocytosis; genome serves as mRNA; polymerase made first; negative strand antigenome is used as template for both progeny genomes and subgenomic mRNA, which encodes the viral capsid and envelope proteins
Term
What does rubella cause?
Definition
mild disease- low grade fever, occasional conjunctivitis, sore throad, lymphadenopathy, morbilliform rash (starts on face and spreads to rest of body)
Term
After exposure to rubella, what is the incubation period like, and when does virus shedding begin to occur?
Definition
7-9 days before virus appears in serium at which point shedding occurs and can be isolated from nasopharynx and stool
Term
When does rubella rash begin?
Definition
16-21 days after initial exposure
Term
Does rubella virus shed after rash disappears or does it stop?
Definition
IMPORTANT: virus continues to shed after rash disappears and can be shed for up to a month after initial exposure (go look at chart)
Term
Where are rubella's most devastating effects seen and what are highest risks?
Definition
fetuses (congenital birth defects aka congenital rubella syndrome): highest risk during 1st and 2nd trimester- usually after 2nd trimester, no CRS (though it has been reported); often spontaneous abortion if infx during 1st month
Term
What are the most common clinical manifestations of maternal fetal infx with rubella if fetus is carried to term?
Definition
mental retardation, motor disabilities, hearing loss, congenital heart disease, cataracts
Term
Are there antiviral treatments for rubella?
Definition
no- not necessary b/c disease is mild
Term
When was rubella vaccine introduced?
Definition
first licensed in 1969 with relatively low incidence in the US since then; epidemics used to occur every 3-9 years
Term
What is rubella vaccine directed towards (in terms of protective purposes)?
Definition
protecting fetus from infx and NOT b/c of disease caused in children or adults (mild disease)
Term
Why is the MMR vaccine such a success?
Definition
all 4 viruses are monotypic (one serotype) and humans are only known reservoir
Term
Which genuses (geni??) are included in Family Parvoviridae?
Definition
Genus parvovirus (ex: Parvovirus B19) and genus dependovirus (ex: adeno-associated virus)
Term
What is the structure of parvoviridae?
Definition
linear, single-stranded DNA (5.6 kilobases); icosahedral capsid; no envelope
Term
Are parvoviridae +/- stranded?
Definition
Equal number of progeny contain either positive or negative strand
Term
Where does replication and assembly occur in parvoviridae?
Definition
nucleius or rapidly dividing cells (provide replication function); note that Parvovirus have autonomous replication while dependovirus require a helper virus
Term
What does Parvo B19 cause?
Definition
erythema infectiosum (mild, common childhood rash)
Term
How much of the adult population is seropositive for ParvoB19?
Definition
50% seropositive; conversion usually after school age; antibodies offer protective immunity
Term
How is Parvo B19 spread?
Definition
via direct contact with respiratory secretions, occurs prior to rash
Term
Describe the pathogenesis of Parvo B19.
Definition
Biphasic: 4 out of 5 will show symptoms; initial viremia may be associated with flu-like symptoms; 2nd phase= rash; symptoms are immune-mediated
Term
What are the 2 phases in the pathogenesis of B19?
Definition
lytic, infection phase AND noninfectious, immunologic phase
Term
What happens during the lytic/infection phase of B19?
Definition
post incubation; decreased reticulocyte and hemoglobin levels; viremia; virus in throat; virus-specific IgG antibody present (starting around day 12) non-specific flu-like symptoms (fever, headache, chills, myalgia); virus is hard to isolate from any site after this time
Term
What happens in noninfectious, immunologic phase of B19?
Definition
decreased reticulocyte and hemoglobin levels; virus-specific IgG antibody present; rash/arthralgia (erythemia infectiosum
Term
What is the "fifth disease?"
Definition
erythema infectiosum: characteristic "slapped cheek" rash; lacy red rash on trunks and limbs (called the 5th disease b/c there are at least 4 other childhood rashes caused by viruses)
Term
What are characteristics of erythema infectiosum?
Definition
"slapped cheeck" rash; lacy red rash on trunks and limbs; resolves in 7-10 days; joint pain or swelling (polyarthritis), flu-like symptoms, less rash in adults
Term
What does Parvo B19 cause in sickle cell patients and how?
Definition
transient aplastic crisis: B19 infects and lyses erythroid precursor cells; results in loss of RC production during infx (7-10 days); shortened life span of RBC in sickle cell patients cannot tolerate absence of precursor pool, results in severe anemia
Term
What happens to immunocompromised patients in B19?
Definition
may develop chronic anemia
Term
Can B19 be transmitted to fetus during pregnancy?
Definition
yes, transplacentally, but most infx are not a concern;5% can result in severe fetal anemia, hydrops fetalis, or miscarriage (most common during 1st half of pregnancy)
Term
How do you diagnose Parvo B19?
Definition
apperance of rash (can be confused with rubella); serological and viral DNA testing of blood
Term
How do you treat Parvo B19?
Definition
treat flu-like symptoms and itchy rash; blood transfusion for anemic patients
Term
How do you prevent Parvo B19?
Definition
difficult to do so b/c infectious period begins before rash; no vaccine; general hygient practices
Term
What viruses are included under family Poxviridae?
Definition
Genus orthopox (Variola virus=smallpox, vaccinia virus-smallpox vaccine); Genus parapox; unclassified agent of molluscum contagiosum
Term
What is the structure of the Poxviridae family?
Definition
non-icosahedral, complex (brick-shaped) structure; can actually be seen under light microscope
Term
Is the Poxiviridae enveloped?
Definition
intracellular has core and lateral bodies surrounded by envelope; extracellular virus has additional envelope
Term
What type of genome does Poxviridae have?
Definition
large, double-strand linear DNA genomes that are complexed with proteins
Term
Where does replication of Poxviridae occur?
Definition
cytoplasmic replication (transcription, dNA synthesis, assembly)
Term
How does Poxviridae replicate in cell?
Definition
virus enters cell, releasing core particle into cytoplasm (uncoating I); core particle contains virus encoded DNA-dependent RNA polymerase, capping and methylating enzymes, and polyA polymerase; early proteins lead to copmlete uncoating (uncoating II); late transcripts and protein (structural proteins and virion enzymes) are produced in cytoplasm leading to virus assmebly in cytoplasm- virus factories; most virions remain intracellular with membrane derived de novo; "crescents" with no detectable contacts with existing membranes begin to envelope core structures; about 1% derive a 2nd envelope from Golgi membrane and are released from cell (extracellular enveloped virus= EEV)
Term
Where does mRNA synthesis occur in Poxviridae?
Definition
a round of early mRNA synthesis proceeds in the core; mRNAs travel to cytoplasm and are translated
Term
What do early proteins in Poxviridae replication do?
Definition
lead to complete uncoating: release DNA into cytoplasm; DNA replication begins in cytoplasm
Term
What are the pertinent infectious agents of Poxviridae in the real world?
Definition
extracellular enveloped viruses (EEVs)
Term
Which 2 Pox viruses specifically cause human disease?
Definition
only 2: variola (smallpox, eradicated in 1977) and agent of molluscum contagiosum (nodular skin lesions)
Term
What Pox viruses CAN cause human disease?
Definition
cowpox lesions on milker's fingers, for example
Term
What is the modern day Pox prototype and what is it used for?
Definition
vaccinia- a lab strain with no known natural reservoir and used for smallpox vaccination
Term
What are the 2 basic forms of smallpox and what is the fatality rate?
Definition
variola major (25% fatality) and variola minor (1% fatality)
Term
Is smallpox systemic or localized?
Definition
systemic with generalized rash
Term
How is smallpox spread?
Definition
inhalation (release from ruptured mouth lesions)
Term
What occurs in the prodrome for smallpox? What follows?
Definition
high fever, malaise, body aches, viremia; followed by small red spots in mouth and on tongue
Term
When is patient most contagious in smallpox?
Definition
when small red spots on mouth and tongue rupture
Term
What happens after 2nd viremia in smallpox (aka toxemic phase)?
Definition
infected macrophages migrated to epidermis, causing lesions (toxemic phase)- initial skin lesion is a raised bump that has a depression in middle; bumps become pustules that feel as if a BB pellet is inside; pustules will scab over, leading to pitted scars; patients is contagious until last scab falls off
Term
How does smallpox conclude?
Definition
death or recovery (accompanied by complete clearance of virus)
Term
How do you distinguish smallpox from chickenpox at initial appearance?
Definition
febrile prodrome (chickenpox does not); firm, well-defined lesions, may develop a pit aka "umbilicated" (chicken pox lesions are superficial); lesions on a given body part will be in the same stage (chickenpox lesions at different stages)
Term
What forms are there of molluscum contagiosum?
Definition
2 forms- childhood and young adulthood form
Term
Describe the chilhood form of molluscum.
Definition
lesions on face, trunk, limbs; spreads by direct skin-to-skin contact; mostly tropical
Term
Describe the adulthood form of molluscum.
Definition
mostly lower abdomen lesions; sexually transmitted
Term
How long does it take for molluscum lesions to disappear?
Definition
2-12 months
Term
How is molluscum diagnosed?
Definition
apperance of lesions and confirmed by large cytoplasmic inclusions in eosinophils of affected area
Term
What is the history of smallpox vaccine?
Definition
Jenner's cowpox starting in 1798; by 1950s, vaccinia had replaced cowpox
Term
What is the vaccine for smallpox like?
Definition
live vaccine; can protect up to 3 days postexposure and up to 7 days can lessen severity; effectiveness wanes after 3 years and completely gone by 20 years
Term
How do you inoculate for smallpox? What happens?
Definition
inoculate in epidermis, produces a localized lesion that heals within 2 weeks
Term
What 4 key features allowed eradication of smallpox by 1977?
Definition
humans were only reservoir; no healthy carriers (virus was eliminated upon recovery); no sub-clinical infections, so cases were readily identified; effective vaccine available
Term
Are there adverse reactions to smallpox vaccine?
Definition
vaccinia is our least safe vaccine:you must screen high-risk people but non-life threatening and life-threatning complications may occur
Term
Who should not receive the smallpox vaccine?
Definition
pregnant/breast-feeding women; immunocompromised people (whether due to heredity, cancer tx, organ transplant, AIDS); those with eczema, atopic dermatitis, severe acne; non-emergent situations for those under 18 years, heart disease patients
Term
What are some non-life threatening complications of smallpox vaccine?
Definition
generalized vaccinia, inadvertent inoculation, erythema multiforme (allergic skin rash)
Term
What are life-threatening complications of smallpox vaccine? (increasing order of frequency)
Definition
progressive vaccinia (associated with CMI defects); postvaccinal encephalitis (autoimmune response?? 30% death rate); eczema vaccinatum (can lead to shock, death); myopericarditis or heart attack
Term
What can you use to treat smallpox vaccine complications?
Definition
vaccinia immune globulin (VIG) or Cidofovir
Term
Even with screening, for every 1 million vaccinees:
Definition
50-1000 will suffer severe adverse reactions; 15 will suffer life-threatening complications; 1-3 will die
Term
What happens when sores in mouth break down during smallpox?
Definition
rash appears on skin (face to extremities)- all parts of body within 24 hours; fever usually falls as rash appears (person feels better)
Term
By 3rd day of rash in smallpox?
Definition
rash becomes raised bumps
Term
By 4th day of rash in smallpox?
Definition
bumps fill with thick, opaque fluid, often with a depression at center- a MAJOR DISTINGUISHING CHARACTERISTIC OF SMALLPOX; fever often rises again at his time
Term
What is the pustular rash in smallpox?
Definition
raised bumps following rash become pustules (sharple raise, round and firm); lasts about 5 days; CONTAGIOUS
Term
What happens after the pustules in smallpox?
Definition
form a crust and then scab; by end of 2nd week after rash starts sores have scabbed over; this stage lasts about 5 days; CONTAGIOUS
Term
Discuss the "resolving scabs" in smallpox?
Definition
This phase lasts about 6 days; scabs fall off, leaving marks on skin that become pitted scars; most scabs will have fallen off 3 weeks after rash appears; CONTAGIOUS UNTIL ALL SCABS HAVE FALLEN OFF
Term
When is person NOT contagious in smallpox?
Definition
when scabs have completely resolved (all have fall off!!)
Term
When is person most contagious in smallpox?
Definition
the early rash (about 4 days); hwen rash first emerges as small red spots on tongue and in mouth (spots develop into sores that break open and spread large amounts of virus into mouth and throat)
Term
What is structure of Family Papvaviridae (sub-families Papiloma, Polyoma, vacuolating virus SV40- monkey)?
Definition
circular double-strand DNA genome (5-8 kilobase pairs) packcaged around a histone; non-enveloped icosahedral cells
Term
What occurs during Papovaviridae replication in permissive cells?
Definition
replication and assembly of progeny occurs in nucleus; virions are released by cell lysis
Term
What occurs during Papovaviridae replication in non-permissive cells?
Definition
infection leads to transformation of cells; polyoma virus genome integrates into host chromosome (can lead to tumor formation)
Term
Polyoma viruses were the first viruses shown capable of transforming cultured cells in vitro. What are 2 transcriptional classes of genes in these viruses?
Definition
Early genes encode three T antigens; late genes encode the structural proteins of the virion
Term
What do the early genes that encode 3 T antigens do in Polyoma virus?
Definition
needed to initate DNA replication; responsible for transformation (analogous to E6 and E7 of papilloma virus; small T and large T antigens are necessary to immortalize cells; small T and middle T antigens needed to transform cells)
Term
What are the 2 known human polyoma viruses and what do they do in hamsters/mice?
Definition
BK and JC viruses; shown to produce tumors in hamsters/mice (DNA from both can transform many non-human cell lines)
Term
Are BK and JC viruses oncogenic in humans?
Definition
NOT oncogenic in humans (permissive host); they are ubiquitous
Term
What is percentage of adult seropositivity of BK and JC?
Definition
> 80% adult seropositivity
Term
What is the percentage of seropositivity of BK and JC in US children?
Definition
BK: 50% of US children by age 3-4 years; JC: 50% of US children by 10-14 years; infection in healthy children is often subclinical!
Term
Where is the site of infection in polyoma virus and what occurs there?
Definition
respiratory or GI tract; initial replication
Term
What happens after initial replication of polyoma?
Definition
followed by viremia and passage to kidney, lung, or brain; viruses persistently infect the kidney
Term
Are polyoma viruses a problem in most adults?
Definition
no, only in immunodeficient hosts: AIDS and transplant patients
Term
Which polyoma virus isfound in urine of AIDS patients?
Definition
BK virus is found but no known disease
Term
What is the etiologic agent of progressive multifocal leukoencephalopathy (PML)?
Definition
JC virus
Term
What is PML?/What causes it?
Definition
progressive demyelinating disease of the CNS probably due to reactivated JC virus that makes its way to CNS and infects and lyses oligodendrocytes; occurs mid to late life
Term
What are symptoms of PML?
Definition
clumsiness, progressive weakness or speech problems in a matter of weeks
Term
How percentage of AIDS patients develop PML?
Definition
2-5%
Term
How do you diagnose PML?
Definition
PCR amplification of JC virus DNA from CSF or brain biopsy; detection of white matter lesions by MRI
Term
What is the prognosis and treatment of PML?
Definition
in transplant patients: alter suppression chemotherapy but still 80% fatality rate within 6 months; in AIDS patients: effective HAART treatment can reduce fatalities to 50%
Term
What is the structure of Herpesvirus?
Definition
icosahedral capsid surrounded by lipid envelope that contains about a dozen virus-encoded glycoproteins
Term
What is the genome of Herpesvirus?
Definition
linear, double-stranded DNA (150-250 kilobase pairs)
Term
Where does the genome of herpesvirus replicated? Where does the virus assemble?
Definition
replicated and assembled in the nucleus
Term
Are herpesvirus infections self-limiting or life-threatening?
Definition
generally: self-limiting in which primary infection is often asymptomatic; life-threatening: especially in immune compromised hosts
Term
What are the alpha herpesvirinae?
Definition
neurotropic for latency, aggressive lytic growth; HSV-1, HSV-2, varicella-zoster virus (VZV)
Term
What are the beta herpesvirinae?
Definition
lymphotropic for latency, more insidious; CMV, human herpesvirus-6 (HHV-6), HHV-7
Term
What are gamma herpesvirinae?
Definition
lymphotropic for latency, more insidious; Epstein-Barr, HHV-8 (Kaposi's sarcoma associated herpesvirus)
Term
What does a primary infection of varicella zoster virus cause?
Definition
chickenpox (varicella)
Term
What is the epidemiology/pathogenesis of varicella zoster?
Definition
highly communicable, spread by respiratory secretions, primarily spread in late winter and early spring
Term
What are the symptoms of varicella zoster?
Definition
fever followed within a day by itchy rash starting on scalp and trunk; lesions appear for up to one week (children may return to school on 6th day after onset of rash); children feel fairly well; adult cases can be more serious (result in pneumonia)
Term
How is diagnosis of varicella zoster made?
Definition
mostly clinical, confirmed by ELISA
Term
How do you treat varicella zoster?
Definition
treat itchiness and aches with calamine lotion, acetaminophen (AVOID ASPIRIN); oral acyclovir; VZV Ig in adults; vaccine
Term
Describe the varicella accine and recommendations for it.
Definition
attenuated virus leading to latent infection; recommended as part of MMR childhood regimen
Term
What happens when varicella is reactivated?
Definition
shingles (zoster)
Term
How often does shingles occur?
Definition
20% of population
Term
Describe the onset of shingles.
Definition
sudden onset of pain and varicella-like rash along thoracic dermatome; rash may last 2-4 weeks with pain lasting longer (postherpetic neuralgia)
Term
How do you treat shingles?
Definition
treat mostly for pain (steroidal); also oral acyclovir
Term
Who gets the zoster vaccine?
Definition
the new vaccine is for the immunocompetent elderly to reduce incidence/severity of zoster
Term
Where is CMV found (in the body)?
Definition
saliva, urine, breast milk, semen, cervical secretions, blood (transplanted organs)
Term
Describe CMV's contagiouness.
Definition
not highly contagious
Term
What is CMV like in low socioeconomic classes?
Definition
infection is at 1-2 years of age with up to 80% of adult population CMV+
Term
What is CMV like in higher socioeconomic classes?
Definition
usually scquired after 16 yaers of age and only about 50% of adult population is CMV+
Term
Which populations are at risk for CMV?
Definition
neonates, day care workers, pregnant workers, gay men, immunocompromised patients (especially transplant patients; AIDS patients susceptible to retinitis, colitis, pneumonia)
Term
What is the pathogenesis of CMV?
Definition
infection through direct contact with secretions, not by aerosol; primary replication is in epithelial cells, followed by spread to lymphoid tissue, CMV latently infects B-cells where it causes large, puffed up lymphocytes
Term
What are the symptoms of neonatal CMV?
Definition
neonatal infx can occur in utero; most are asymptomatic but can result in retardation and deafness
Term
What the symptoms of adult CMV?
Definition
asymptomatic though mononucleosis accompanied by fever can occur
Term
Who is especially at risk with CMV?
Definition
immunocompromised hosts: most organ transplant patients get CMV infx with pneumonitis (most severe outcome about 1-4 months after transplant, preceded by fever); may be caused by CMV+ donor or by reactivation of CMV+ recipient; if you hear transplant patient, think CMV!!!! Also, AIDS patients prone to CMV retinitis, colitis, pneumonitis
Term
What can you do to help immunocompromised patients receiving a transplant (in regards to CMV)?
Definition
prophylactic tx with CMV Ig and ganciclovir looks promising for limiting complications
Term
How do you diagnose CMV?
Definition
ELISA; shell vial assay in which indirect immunofluorescence is used to detect an immediate early protein after 24 h of cell culture infx
Term
How do you treat CMV?
Definition
ganciclovir, a guanosine analog similar to acyclovir, or ciofovir, a deoxycytidine analog
Term
What does ganciclovir require?
Definition
as with ACV, requires phosphorylation by viral kinase; triphosphate form preferentially inhibits CMV polymerase but is more toxic to host than ACV
Term
What are the side efects of ganciclovir?
Definition
neutropenia and GI tract bleeding
Term
For whom is ganciclovir approved?
Definition
treatment of transplant patient infx, CMV retinitis tx in AIDS patients
Term
What else is approved for CMV retinitis in AIDs patients?
Definition
foscarnet
Term
What is the MOA for cidofovir?
Definition
competitive inhibitor of CMV (and HSV) DNA polymerase but does not require viral kinase action for activity
Term
What is cidofovir approved for?
Definition
CMV retinitis tx in AIDS patients
Term
When does infection of Epstein-Barr occur?
Definition
early age in low socioeconomic setting; adolescence and early adulthood in higher socioeconomic setting (may lead to infectious mononucleosis)
Term
How much of the adult population contains Ab to EBV?
Definition
90-95%
Term
What can EBV cause in immunocompromised hosts?
Definition
oral hairy leukoplakia in immunocomprosed hosts
Term
What is hairy leukoplakia?
Definition
productive infection of tongue epithelial cells; rarely seen except in AIDS patients; treated with ACV
Term
What does EBV cause in some transplant patients?
Definition
posttransplant lymphoproliferative disease (PTLD)
Term
With which lymphoma/carcinoma is EBV associated?
Definition
Burkitt's lymphoma and nasopharyngeal carcinoma
Term
What is the pathogenesis of EBV?
Definition
saliva by kissing with incubation period of 4-7 weeks; initial replication in oropharyngeal epithelium; spreads to lymphocytes then to liver and spleen; EBV remains latent in throat epithelium and B cells; oral shedding of virus occurs for many weeks
Term
What are the symptoms of EBV?
Definition
most asymptomatic except infectious mononucleosis presents with sore throat, fever for 1-2 weeks, malaise, lymphadenopathy with uneventful recovery
Term
How do you diagnose EBV?
Definition
based on symptoms and presence of at least 50% atypical, large lymphocytes with lobulated nuclei; may also look for heterophil antibodies (Monospot test)
Term
Explain the heterophil Ab (Monospot test).
Definition
Ab agglutinate sheep RBC; not present in all patients and origin not understood; if present, will distinguish EBV mono from CMV mono
Term
EBV and PTLD
Definition
uncontrolled proliferation of B cells due to transformation by EBV and absence of CTLs to control them; highest risk in seronegative transplant recipients in their 1st year; treat by STOPPING immunosuppression (monitor for rejection; ACV not useful b/c infx is latent, virus not replicating)
Term
EBV and Burkitt's lymphoma
Definition
neoplasm of B cells that affect bones of jaw; endemic in central Africa and New Guinea; associated with 3 factors: early EBV infx leading to latency, activation of c-myc, malaria; early detection allows cure rate of 80%; ouside of Africa, only 20% of BL patients have EBV genomes in tumor
Term
EBV and nasopharyngeal carcinoma
Definition
neoplasm of epithelial cells; association with EBV is worldwide; high frequency in southern China: high salt diet is likely a cofactor; initial presentation is painless lump in neck; at best, only 60% of patients survive 10 years
Term
EBV is also liked to?
Definition
Hodgkin's lymphoma? Multiple sclerosis?
Term
What does human herpesvirus-6 (HHV-6) cause?
Definition
roseola (exanthem subitum) and acute febrile illness
Term
When does HHV-6 usuall infect?
Definition
between ages of 6 months to 3 years
Term
How much of the US population has Ab to HHV-6?
Definition
97.00000%
Term
When do HHV-6 infections usually occur (what time of year)?
Definition
late spring, mid-autumn
Term
Pathogenesis of HHV-6?
Definition
not well worked out but incubation period is thought to be about 10-15 days
Term
What is the principal symptom of HHV-6?
Definition
high fever (104°F or higher)
Term
What are the symptoms like in HHV-6?
Definition
as few as 25% show rash; other symptoms similar to rubella
Term
How do you characterize treatment of HHV-6?
Definition
supportive
Term
Is there link between HHV06 and MS patients?
Definition
possibly- increased anti-HHV-6 IgM titers
Term
What does HHV-7 cause?
Definition
roseola
Term
How much of the US population is seropositive to HHV-7 by early childhood?
Definition
95.00000%
Term
What is the relation between HHV-8 and Kaposi's sarcoma?
Definition
the virus is necessary but not sufficient to cause KS
Term
How is the relation between HHV-8 and KS quantified?
Definition
DNA sequences of HHV-8 recovered from AIDS and non-AIDS KS patients; >80% seropositivity among KS patients, <5% among US blood donors (low risk group)
Term
Describe the B cell tropism in HHV-8.
Definition
KS tumors occur in lining of lymphatic system; lymphatic channels fill with blood cells, hence bluish, bruised appearnce of lesions
Term
Where is classical KS seen?
Definition
mediterranean population and Sub-Saharan Africa- not sexually transmitted in these cases
Term
What are most KS patients in the US?
Definition
AIDS patients- sexually transmitted but virus is absent from semen and vaginal secretions
Term
Where is HHV-8 virus present in KS/AIDs patients?
Definition
saliva- not understood how it is sexually transmitted
Term
What is the incubation period for KS after HHV-8 infx?
Definition
10 years- may be relatively mild but if patient is severely compromised, can be life threatening
Term
What other B cell abnormalities are caused by HHV-8?
Definition
primary effusion lymphoma, Castlemen's disease
Term
Is HHV-8 symptomatic in AIDS/Non-AIDS forms?
Definition
95% are ASYMPTOMATIC; infection must be accompanied by loss of immune system for disease symptoms- old age in classical forms and AIDS in gay populations; if symptomatic, treatment in AIDS patients Is tumor-specific (resection, chemotherapy) or targets HIV but not HHV-8
Term
Which viruses (from the polyoma/herpesvirus lecture) are ubiquitous (>80% seropositivity) in all US populations?
Definition
VZV, EBV, HHV-6, HHV-7
Term
Which viruses (from the polyoma/herpesvirus lecture) are typically acquired in early childhood by essentially all US populations and/or typically symptomatic during primary infx?
Definition
VZV, HHV-6, HHV07
Term
Which viruses (from the polyoma/herpesvirus lecture) sexually transmitted?
Definition
HSV-2, HSV-1, CMV, HHV-8
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