Retroviruses, HIV and AIDS Flashcards
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
what do most retroviruses cause
leukemias and sarcomas
What are acute transforming viruses
retroviruses that carry intact oncogenes with genome
What enzyme to retroviruses have to incorporate viral genome into hose
integrase
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)
what are non-acute transforming viruses
activate host pro to-oncogenes by integrating viral DNA into key regulatory area
What would you have high on Ddx if patient from tropics has tropical spastic paraparesis
Human T cell leukemia virus I
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)
What 3 enzymes must HIV have
protease, reverse transcriptase and integrase
What surface glycoproteins are on HIV
gp120 and 41
What are the long terminal repeats in retroviruses
sticky ends and have promoter/enhancer functions
What genes are encoded on all retroviruses
gag
pol
env
What additonal genes does HIV encode for besides gag pol env
tat, rev, nef, vif, vpr, vpu
what gene codes for the major structural proteins in retroviruses and what are these proteins
gag(Group Ag)
Nucleocapsid, capsidAg(p24) and matrix proteins
What gene encodes for retroviral enzymes
pol
What does env encode for in retroviruses
envelope proteins that form glycoprotein spikes gp 120 and gp41 (gp160 and bind to CD4 T cells)
What are the early proteins in HIV
tat, rev and nef
What are the late proteins in HIV
vif, vpr, vpu
What does tat encode
Transactivator protein that binds genome and activates transcription
what does rev encode
binds to env to decrease splicing so increases reading of gag, pol and env to increase virions
what does nef encode
down regulates CD4 and MHC class I to escape CTL killing
What does vif encode
required for ds DNA to be produced from HIV RNA genome
also blocks APOBEC3 enzymes
What are the APOBEC enzymes
that break down newly made viral DNA
What does vpr encode
Viral protein R that regulates nuclear import of HIV-1 and is required for viral replication in non-dividing cells
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
