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9.26 Retroviruses
8am by Dr. Amedee
90
Microbiology
Professional
09/27/2011

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Cards

Term
What does reverse transcriptase do?
Definition
converts ssRNA into ssDNA then to ds DNA (integration of viral genome into host DNA)
Term
What are the four subfamilies of retroviruses?
Definition
lentivirus, oncovirus, spumavirus, and endogenous retrovirus
Term
What are the four subfamilies of retroviruses?
Definition
lentivirus, oncoviruses, spumaviruses, endogenous retroviruses
Term
What are HERVs?
Definition
human endogenous retroviruses. retrovirus sequence integrated into the human genome and transmitted vertically (~1% of the human genome)
Term
T/F HERVs can produce infectious particles.
Definition
false, although some have open reading frames capable of encoding functional proteins
Term
Where is the HERV-W envelope protein expressed? What is it's purpose?
Definition
human placenta (syncytin protein); essential to create and maintain the syncytiotrophoblast layer between maternal and fetal circulation (essentially a retroviral fusion and entry protein)
Term
How does syncytin mediate fusion?
Definition
exactly the same was as influenza, measles, HIV, Ebola, lassa fever, and sars! binding induces the N and C helices to clamp together and the hyrdophobic fusion and aromatic peptides cooperate to induce cell fusion
Term
What is an example of a human spumavirus?
Definition
human foamy virus
Term
What is an example of a human oncovirus?
Definition
HTLV-1 and II
Term
What are examples of human lentivirus?
Definition
HIV1 and 2
Term
Describe the genome and outer covering of retroviruses.
Definition
icosahedral, envelolped with two identical copies of single-stranged + RNA
Term
What is the general genetic organization of retroviruses?
Definition
LTR-gag-pol-env-LTR
Term
What is the gag gene?
Definition
group-specific antigen gene; encodes capsid, nucleocapsid and matrix proteins
Term
What is the pol gene for?
Definition
polymerase gene; encodes the enzymes reverse transcriptase, protease and integrase
Term
What is the env gene for?
Definition
envelope gene; encodes surface and transmembrane proteins
Term
What are the LTRs for?
Definition
long terminal repeats; gene sequences that bind cellular and viral transcription factors (promoters and enhancers)
Term
How does HIV progeny exit the host cell?
Definition
viral budding
Term
What happens to the retroviral genome after entry to host cell?
Definition
linear viral RNA is reverse-transcribed ds DNA circle in the cytoplasm. After nuclear localization, genome integrates into host genome via LTRs and integrase
Term
Where does retroviral RNA replication occur?
Definition
in the cytoplasm
Term
When are teh LTRs generated?
Definition
after retroviral RNA replication in teh cytoplasm
Term
What's another name for the viral genome once it is part of the host genome?
Definition
provirus
Term
T/F Spumaviruses can be oncogenic.
Definition
false! but they do establish persistent infections
Term
T/F Spumaviruses have been isolated only from humnas.
Definition
false! isolated from many animal species including humans
Term
What is the diseaes caused by spumaviruses?
Definition
considered non-pathologic/no disease associated in humnas
Term
Describe the distinct cytopathology of spumaviruses.
Definition
foamy or lace-like appearance and are often accompanied by syncytium formation
Term
What are oncoviruses?
Definition
retroviruses that immortalize or transform cells. Have different core and capsid morphology. May contain growth -regulating oncogenes (sis, ras, src, mos, myc,jun, fos) which are almost identical to the cellular porteins involved in celllular growth control.
Term
HTLV causes what diseases?
Definition
adult T cell leukemia and tropical spastic paraparesis
Term
Where is HTLV-1 endemic?
Definition
southern Japan and the Caribbean
Term
How is HTLV-1 transmitted?
Definition
Transmission requires cell to cell contact: sexually, mother-to-infant (breast feeding), IVDU
Term
How long after infection does HTLV-1 cause cancer?
Definition
20-30 years later
Term
What percent of HTLV-1 infected people get ATLL?
Definition
~2%
Term
Name the non-neoplastic neurologic d/os caused by HTLV-1.
Definition
HTLV-1 associated myelopathy (tropical spastic paraparesis) or HTLV-1-associated myelopathy (HAM) (this is a demyelinating diseaes of the brain and spinal cord-motor neurons)
Term
What oncogene does HTLV contain?
Definition
HTLV doesnt have an oncogene, instead it has "tax" a transcriptional regulator (binds in LTR). Also, activates specific cellular genes (IL-2 and GMCSF) to promote outgrowth of that cell.
Term
What are "flower cells"?
Definition
multilobulated lymphocytes seen in the blood smear of patients with adult T cell leukemia caused by HTLV-1
Term
Describe the surface, transmembrane, matrix, capsid and nucleocapsid proteins of HTLV-1 virion.
Definition
surface- gp 46
transmembrane- gp 21
matrix- p19
capsid- p24
nucleocapsid is p15
Term
Where is HTLV-II prevalent?
Definition
worldwide in IVDU
Term
What diseases are associated with HTLV-II?
Definition
its unclear; some neurologic and chronic pulmonary d/os
Term
Where is HTLV-3 and 4 found?
Definition
small number of patients in Cameroon
Term
How do you diagnose HTLV?
Definition
EIA- detection of antibodies against viral antigens; there is cross-reactivity between HTLV I and II
Term
How do you treat HTLV infection?
Definition
ATLL (anti cancer therapy)
HAM/TSP (antiretrovirals)
Term
What characterizes lentiviruses?
Definition
slow onset of disease and neurologic d/os and immunosuppression
Term
What are some nonhuman examples of lentiviruses?
Definition
SIV, visna virus (sheep), caprine arthritis/encephalitis virus (goats)
Term
What is the matrix protein of HIV?
Definition
p17
Term
What is the envelop protein of HIV?
Definition
gp 120 env (gp 41)
Term
What is the matrix and capsid protein of HIV?
Definition
matrix: p17, capsid is p24
Term
Which HIV is less virulent?
Definition
HIV-2
Term
Where do you find HIV-2?
Definition
sporadic cases currently outside of west africa
Term
Are the antigens to HIV-1 the same as those to HIV-2?
Definition
core antigens cross-react but envelope antigens to not
Term
What virus did HIV-2 originate from?
Definition
sooty mangabe SIV
Term
When are gag and gag-pol peptides cleaved?
Definition
following release of the virion from the cell
Term
Which enzymes are located in the HIV virion?
Definition
reverse transcriptase and integrase
Term
What are the functions of reverse transcriptase?
Definition
RNA-dependent DNA polymerase, polypurine endonuclease, RNA-DNA hybrid RNase, ssDNA-dependent DNA polymerase
Term
Is reverse transcriptase a dimer, trimer, or tetramer?
Definition
dimer
Term
T/F gp 160 is a trimer.
Definition
true! gp 160 precursor proteins are cleaved by cellular proteases and assembled as trimers
Term
How many glycosylation sites are in gp 120?
Definition
30-38 N-linked glycosylation sites
Term
What are the essential regulator genes of HIV?
Definition
tat, rev, and nef
Term
What is tat?
Definition
protein that is positive regulator of transcription by control of elongation by RNA polymerase II
Term
What is rev?
Definition
protein that regulates exprsesion of viral mRNA for structural genes. Binds to RRE and promotes the nuclear export, stabalization, and utilization of the viral mRNAs containing RRE
Term
What is nef?
Definition
regulatory gene of HIV that produces a protein needed for high levels of virus associated with disease progression; down-regulates CD4 and MHC class I molecules. Not necessary for replication but necessary for disease
Term
What are the "accessory" genes of HV?
Definition
vif, vpr, vpu (HIV1 only), and vpx (HIV2 only)
Term
What is VIF?
Definition
viral infectivity factor; required for HIV-1 replication in primary cells; prevents the action of the cellular APOBEC-3G protein, which deaminates DNA:RNA heteroduplexes in the cytoplasm
Term
What is vpr?
Definition
proposed functions include targeting nulcear import of preintegration complexes, cell growth arrest, transactivation of cellular genes, and induction of cellular differentiation
Term
What is the function of vpu?
Definition
integral membrane protein; degrades CD4 in ER and enhances virion release
Term
What is vpx?
Definition
homolog of HIV-1 vpr (integral membrane protein; degrades CD4 in ER, and enhances virion release)
Term
Breifly describe the HIV replication cycle.
Definition
1) atatchment 2) fusion 3-4) RT--dsDNA 5) transport to nucleus 6) integration 7) viral mRNA 8-9) viral proteins 10) assembly of virions 11) protease cleavage-mature particles
Term
What is the risk of infection per sexual encounter with an HIV+ individual?
Definition
1:100 to 1:10,000
Term
Why are some people resistant to HIV infection?
Definition
sex workers have some unkown immune response and other individuals have a non-functional CCR5 protein receptor
Term
What percent of caucasians have the CCR5 deletion?
Definition
10% heterozygous, 1% homozygous
Term
What immune dysfunctions are associated with the CCR-5 mutation?
Definition
none
Term
What are two independent predictors of AIDS progression?
Definition
CD4+ T cell count and viral load
Term
What dictates the kinetics of the CD4+ T cell decline and time to development of clinical AIDS?
Definition
the viral set point after acute infection
Term
Where is the AIDS virus at the time of acute HIV syndrome?
Definition
widely disseminated, seeding of lymphoid organs
Term
How do you tell if an HIV+ pt has AIDS?
Definition
clinical component + immunologic component
Term
HIV infection destroys massive amounts of CD4 cells each day before symptoms manifest?
Definition
true, body is able to keep up but gradual overall loss of CD4 cells eventually will lead to immune dysfunction
Term
T/F > 90% of CD4+ cells are infected by HIV.
Definition
False! Altho >90% are destroyed by HIV, significantly less are actually infected.
Term
How does HIV kill CD4 T cells?
Definition
syncytia formation (on infected cell can fuse with unifected cells) and apoptosis
Term
How does HIV kill CD4 T cells?
Definition
syncytia formation (on infected cell can fuse with unifected cells) and apoptosis
Term
How does HIV evade CTL response and antibody response?
Definition
exiting as a quasispecies= antigenic drift of gp 120 (highly variable regions of envelope) and glycosylation of gp 120
Term
CD4 loss in HIV infection is mainly due to...
Definition
apoptosis
Term
How does HIV causes apoptosis of CD4 cells and other cells?
Definition
pro-apoptotic HIV proteins, apoptosis induced by death receptors, massive apopuosis in GALT releases circulating microbial products that causes apoptosis
Term
Which HLA types are associated with slower AIDS disease progression?
Definition
HLA B 27 and HLA B 57
Term
How do you define an AIDS long term non progressor/elite controller?
Definition
no clinical evidence of progression in > 10 years. Patients have low viral loads and high CD4 cell counts. Lymph node architecture is intact and have vigorous CD8+ cytotoxic T cells against HIV. Have elevated titers of neutralizing antibodies
Term
Whta does NRTI stand for? NNRTI?
Definition
nucleoside analog reverse transcriptase inhibitor (NRTI) non-nucleoside analog reverse trancriptase inhibitors (NNRTI)
Term
What are the different classes of antiretrovirals?
Definition
CCR5 inhibitors, fusion inhibitor, NRTI, NNRTI, integrase inhibitor, protease inhibitor
Term
What are the major limitations of nucleoside analogs?
Definition
their toxicity, lack of activity in some cell types, and susceptibility to viral resistance
Term
What two drugs used in combination are the most effective anti-HIV therapies developed to date?
Definition
protease inhibitors used in combination with reverse transcriptase inhibitors (NRTI and NNRTI)
Term
Why are HIV drugs used in combination with each other?
Definition
substantially reduces the likelihood of protease or multiple-resistant HIV strains developing
Term
What was the Merck Vaccine Trial (STEP)?
Definition
adenovirus vector with gag, pol adn nef. Did not prevent HIV1 infection or reduce viral loads in those infected
Term
What was the THailand study HIV vaccine?
Definition
canarypox vector- prime boost strategy with 6 immunizations over 6 months. ALVAC-HIV canarypox vector with HIV env, gag and pro. AIDSVAX-B/E is composed of geneically engineered gp 120, subtypes B adn E
Term
What is pre-exposure HIV prophylaxis?
Definition
once daily tenofovir or once daily tenofovir plus emtricitabine (NRTI)
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