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Flashcards in HIV - retroviruses Deck (56):
0

Kaposi's Sarcoma

relatively benign cancer usually seen in elderly
but cases were starting to present in 1981 in young gay men

1

Pneumocystis Carinii Pneumonia

rare lung infection
pts usually cured in 1 ten day treatment or died
but pts were asking for refills
clustering of these cases

2

AIDS defined by CDC in

september of 1982

3

1983

science realized that HIV-1 is causative agent of AIDS

4

retroviruses

enveloped
+ssRNA
that replicate through DNA intermediate using reverse transcriptase

5

Deltaretrovirus

complex
Oncovirinae
causes Human T cell leukemia

6

Lentivirus

complex
Lentivirinae
HIV-1, HIV-2, FIV

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retroviruses encode

RNA dependent DNA pol transcriptase

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Retroviruses replicate through

a DNA intermediate termed Provirus

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How is provirus integrated into the host genome?

with help of integrase

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What genes do simple retroviruses encode?

gag
pol
env

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Complex retroviruses encode

accessory genes
tat
rev
nef
vif
vpr
vpu

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what enzymes does GAG encode?

MA
CA
NC

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MA

matrix protein that lines the envelope

14

CA

capsid protein
protects the core
most abundant

15

NC

Nucleocapsid protein
protects the genome
forms the core

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Proteins that POL encodes?

RT
IN
PR

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RT

reverse transcriptase
transcribes RNA genome
has RNAseH activity

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IN

integrase protein
encoded by pool gene
needed for integration of provirus

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PR

protease
essential for gag protein cleavage during maturation

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ENV encodes proteins

SU
TM

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SU

surface glycoprotein
outer envelop glycoprotein
major virus antigen

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TM

Transmembrane Protein
inner component of mature envelope glycoprotein

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TAT

transactivator
positive regulator of transcription

24

REV

regulation of viral expression
allows export of unspliced and partially spliced transcripts from nucleus

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VIF

viral infectivity
affects particle infectivity

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VPR

viral protein R
transport of DNA to nucleus, augments virion production
cell cycle arrest

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VPU

viral protein U
promotes intracellular degradation of CD4 and enhances release of virus from cell membrane

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NEF

negative regulation factor (not one of the regulatory proteins)
augments viral replication in vivo and in vitro
Downregulates CD4 and MHC II - this protects virus during replication so that cell does not shut down

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steps of Retrovirus replication - 7 steps

1 - fusion of HIV to host cell surface
2 - HIV RNA, RT, integrase and other proteins enter the cell
3 - Viral DNA is formed by RT
4 - Viral DNA is transported across the nucleus and integrates into host DNA
5 - New viral RNA is used as genomic RNA and to make viral proteins
6 - New viral RNA and proteins move to the cell surface and a new immature HIV forms
7 - virus matures by protease releasing individual HIV proteins

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HTLV-1 clinical manifestations - Myelopathies

Tropical spastic paraparesis
Inflammation, spinal cord atrophy
affects age 30-50, slow development
leg weakness
Hyperreflexia
Urinary and fecal incontinence

31

HTLV-1 clinical manifestations - Motor disorders

ALS-like symptoms
weakness and muscle fasciculation
affects the anterior gray horn and ventral root nerves

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HTLV-1 clinical manifestations Adult T cell leukemia/lymphoma

Rare, several lymphocytes with irregular nuclei
5% of infected present with ATLL
Tap gene, IL-2 >>T cell proliferation
Lymphadenopathy, rapidly fatal without treatment

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HTLV-1 clinical manifestation in childern

Infective dermatitis is chronic relapsing syndrome

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HTLV-2 clinical manifestations

associated with atypical T cell hairy Leukemia
Subtype of Chronic Lymphoid Leukemia - abnormal B lymphocytes
-Pancytopenia
-Easy bruising
-Fatigue

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HIV-1 classification

Major group - M
Outlier group O
new groups N
new groups P

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Group M HIV-1

>90% of all HIV-1 infections
9 genetically distinct subtypes
A-K

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HIV-2

has an extra accessory protein over HIV-1
8 groups: A-H
A and B most common

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HIV infects cells that carry the receptor and co receptors

CD4
CCR5
CXCR4

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CD4 expressed on

surface of CD4 T lymphocytes (helper T lymphocytes) and macrophages (including dendritic cells)

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CCr5 expressed on

CD4+ T lymphocytes and on macrophages

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CXCR4 expressed on

CD4+ T lymphocytes and T cell lines

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M-Tropic

R5 viruses
Macrophage tropic
infects Macrophage and CD4+ T lymphocyte

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T-Tropic

X4 viruses
T cell tropic
infects CD4+ T lymphocytes and CD4+ T cell lymphoblastoid cell line

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Risk assessment screening guideline

Very high risk: MSM (males having sex with males) injection drug users
High risk: having acquired or request testing for STIs

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Behavioral Risk Factor Screening guidelines

unprotected vaginal or anal intercourse
sexual partner who is HIV+, bisexual or injection drug user
exchanging sex for money or drugs

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Screening in general is performed for these groups

all patients aged 13-64 years
All pts initiating treatment for TB should be screened routinely for HIV infection

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what are some lab diagnostic tests for HIV?

2 step diagnosis- serum ELISA followed by western blot or immunoflour
Alternate tests for initial diagnosis - rapid oral antibody test, results in 5-40 mins
FDA-approved tests for initial and confirmatory diagnosis - combination tests (p24 antigen plus HIV antibodies)
Qualitative HIV-1 RNA (to detect presence of virus)

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Lab diagnosis test for Post diagnosis

Quantitation of virus in blood: HIV-1 RT-PCR
Early marker of infection: Western Blot for p24 antigen
Correlate of HIV disease: CD4/8 T cell ratio

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Refer to slide with HIV western blot
what is a negative result?
what is a positive result?

Negative - Total absence of bands associated with HIV-1 or WHO guidelines say weak p17 is also negative
Positive - presence of at least 2 of following bands: p24, gp41, and gp120/160

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During acute infections, pts will develop

non specifc viral illness
lymphadenopathy
fever
fatigue
rash
that usually lasts about 1-2 weeks

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How is acute HIV diagnosed?

acute HIV infection is time between infection and seroconversion
documented evidence of detectable HIV RNA or DNA or of p24 antigen in plasma or serum in presence of documented negative or indeterminate result from an HIV antibody test is required for a diagnosis of acute HIV infection

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Steps of HIV binding

1. HIV gp120 binds to T cell CD4
2. conformational change in gp120 promotes binding to chemokine receptor
3. conformational change in gp41 exposes fusion peptide, which inserts into T cell membrane
4. Fusion of viral and cell membranes

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What are the 3 structural genes?

ENV - gp120 and gp41
GAG - p55, p40 and p24
POL - reverse transcriptase, protease, integrase

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What are the 2 regulatory proteins?

TAT
REV

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what are the 4 accessory proteins?

VIF
VPR
VPU
NEF