Retroviruses, HIV and AIDS Flashcards by Amanda Beach

What are the 3 unique big picture conceps of retroviruses

that they have reverse transcriptase
they can activate pro to-oncogenes
they can destroy CTLs

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what do most retroviruses cause

leukemias and sarcomas

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What are acute transforming viruses

retroviruses that carry intact oncogenes with genome

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What enzyme to retroviruses have to incorporate viral genome into hose

integrase

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what are defective acute transforming viruses

retroviruses that have lost own RNA needed for replication so need coinfecting virus to cause cancer(if obtained oncogene)

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what are non-acute transforming viruses

activate host pro to-oncogenes by integrating viral DNA into key regulatory area

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What would you have high on Ddx if patient from tropics has tropical spastic paraparesis

Human T cell leukemia virus I

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What is the structure of HIV

spherical enveloped virus with central cylindrical nucleocapsid
2 ss RNA pieces with a nucleocapsid proteins and 3 essential enzymes
icosahedreal symmetry with capsid proteins (p24)

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What 3 enzymes must HIV have

protease, reverse transcriptase and integrase

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What surface glycoproteins are on HIV

gp120 and 41

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What are the long terminal repeats in retroviruses

sticky ends and have promoter/enhancer functions

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What genes are encoded on all retroviruses

gag
pol
env

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What additonal genes does HIV encode for besides gag pol env

tat, rev, nef, vif, vpr, vpu

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what gene codes for the major structural proteins in retroviruses and what are these proteins

gag(Group Ag)

Nucleocapsid, capsidAg(p24) and matrix proteins

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What gene encodes for retroviral enzymes

pol

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What does env encode for in retroviruses

envelope proteins that form glycoprotein spikes gp 120 and gp41 (gp160 and bind to CD4 T cells)

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What are the early proteins in HIV

tat, rev and nef

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What are the late proteins in HIV

vif, vpr, vpu

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What does tat encode

Transactivator protein that binds genome and activates transcription

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what does rev encode

binds to env to decrease splicing so increases reading of gag, pol and env to increase virions

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what does nef encode

down regulates CD4 and MHC class I to escape CTL killing

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What does vif encode

required for ds DNA to be produced from HIV RNA genome

also blocks APOBEC3 enzymes

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What are the APOBEC enzymes

that break down newly made viral DNA

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What does vpr encode

Viral protein R that regulates nuclear import of HIV-1 and is required for viral replication in non-dividing cells

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What does vpu encode

downregulates CD4 and MHC I expression on cell surfaces and facilitates HIV virion release from cells

Why is HIV so hard to create a vaccine against

has highest mutation rates in many of its components

What group of HIV is responsible for majority of worlds HIV

Group M

What area is subtype HIV B common in

North America and Europe

How is HIV spread

parenteral route

Why are you more prone to HIV is have concurrent STD

the already there inflammation increases change of HIV-laden macrophages and lymphocytes

What are the risks from needle prick to contract HIV? Hep B? Hep C?

HIV 0.3% Hep B 30% Hep C 3%

what other cells besides T helper cell shave CD4 R

macrophages, monocytes, dendritic cells

What must the cell have for fusion and translocation of HIV into host

co R CCR5 or CXCR4

What proteins from lymphocytes inhibit HIV infection by binding CCR5

RANTES MIP1-alpha MIP1-beta

where is viral RNA reverse transcribed into DNA

cytoplasm

What are the 3 stages after HIV infection

acute viral illness a clinical latency AIDS

describe acute viral illness from HIV

like mononucleosis: fever, malaise, lymphadenopathy, pharyngitis) high levels blood bourne HIV that infect lymph nodes and macrophages

describe clinical latency from HIV

median of 8 years no symptoms but general lymphadenopathy steady gradual destruction of CD4 T cells at end more susceptible to bacterial infections and have systemic symptoms like fever, weight loss, night sweats and adenopathy

Define AIDS and average lifespan

live about 2 years CD4 count less than 200 with serologic evidence of HIV many opportunistic infections-AIDS related

What are the AIDS related opportunistic infections

Candida esophagitis, pneumocystis carinii pneumonia and Kaposi's sarcoma

What are normal CD4 counts and how steadily do they decline in HIV

1000 is normal, decline 60 cells/ulblood/year

what are symptoms of CD4 count around 400-200

``` weight loss, fever, night sweats, adenopathy skin infections(candida) bacterial infections (M TB) ```

What type of infections occcur in patients under 200 ul

Pneumocystitis carinii pneumonia Cryptococcus neoformans Taxoplasma gondii

What infection (rare to humans) occurs in AIDs patients with CD4 less than 50

Mycobacterium avium-intracellulare MAC | CMV also

What are the best predictor of opportunistic infections in HIV patient

CD4 counts

The viral load of HIV can tell you what about the disease

how quickly the CD4 are dropping

How do infected T cells form multinucleated giant cells

the gp 160 fuse together

How are uninfected bystander CD4 T cells destroyed in HIB

from Fas mediated mechanism as result HIV proteins being released open and sitmulating apoptosis

How are B cells affected by HIV

polyclonal activation causing hypergammagloculinemia causing IC formation and autoAbs

What cells are not destroyed by HIV but rather are reservoirs

monocytes and macrophages

What are the widespread symptoms from AIDS

night sweats, fevers, lymphadenopathy and severe weight loss

What type of meningitis occurs with AIDS

aseptic

What type of malignancies are common in AIDS

B cell lymphoma(with EBV) Kaposi's sarcoma HHV-8 non-hodgkins lymphoma, cervical cancer and anal intraepithelial neoplasia

What does kaposi's sarcoma look like

red to purple lesions that are plaques or nodules and all over the body

What does MAC cause

smoldering wasting disease fever, night sweats, weight loss and diarrhea elevated liver function tests Fever of unknown origin in AIDS

What type of fungal infections do AIDS patients suffer from

candida albicans cryptococcus neoformans histoplasma capsulatum and cocidoides immitis pneumocystis jiroveci pneumonia (PCP)

what does cryptococcus neoformans cause in AIDS pateitns

meningitis fever, nausea, vomiting not meningeal inflammation- may just be fever HA, mental status changes, fever.

what does histoplasma capsulatum and coccidoides immitis cause in AIDS patients

disseminated disease in meninges, lungs skin and other areas

What is the most common opportunistic infection in US among AIDS patients

PCP or PJP cough and hypoxia CXR interstital infiltrates or normal

What viral infections are common in AIDS patients

Herpes Zoster EBV Herpes simplex CMV

what does herpes zoster look like in AIDS patients

non dermatomal zoster

what does EBV cause in AIDS patients

oral hairy leukoplakia | white hairlike projections from side of tongue(will not rub off like thrush)

What does CMV look like in AIDS patients

chorioretinitis and blindness | dysphagia and diarrhea

What protozoal infections are common in AIDS patients

toxoplasma gondii | Cryptosporidium, Microsporidia an dIsosporabelli

Toxoplasma gondii causes what in some AIDS patients

lesions in the brain | fever, HA, focal neurologic deficits like seizures

what do the other protozoal parasites cause in AIDS patients

chronic diarrhea

When can viral RNA Ag like p24 be detected after HIV exposure

in weeks

When can Ab agains HIV Ag be detected after exposure

3-6 weeks

What is used to confirm HIV Dx

western blot after +ELISA

What proteins are checked in western blot for HIV

gag, pol and env

What is a + western blot for HIV

if has 2 HIV gene products | p24, gp41 and gp120

are the rapid HIV tests confirmatory

no even though super specific and sensitive, must have western blot pulled

in the 3-6 week incubation period after HIV exposure what will clinicians do for Dx

measure HIV RNA with PCR

What is HAART

Highly Active Antiretroviral Therapy | use of 3 drug therapies