HIV - retroviruses

Question 0

Pneumocystis Carinii Pneumonia

Answer 0

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

Question 1

Kaposi’s Sarcoma

Answer 1

relatively benign cancer usually seen in elderly

but cases were starting to present in 1981 in young gay men

Question 2

AIDS defined by CDC in

Answer 2

september of 1982

Question 3

1983

Answer 3

science realized that HIV-1 is causative agent of AIDS

Question 4

retroviruses

Answer 4

enveloped
+ssRNA
that replicate through DNA intermediate using reverse transcriptase

Question 5

Deltaretrovirus

Answer 5

complex
Oncovirinae
causes Human T cell leukemia

Question 6

Lentivirus

Answer 6

complex
Lentivirinae
HIV-1, HIV-2, FIV

Question 7

retroviruses encode

Answer 7

RNA dependent DNA pol transcriptase

Question 8

Retroviruses replicate through

Answer 8

a DNA intermediate termed Provirus

Question 9

How is provirus integrated into the host genome?

Answer 9

with help of integrase

Question 10

What genes do simple retroviruses encode?

Answer 10

gag
pol
env

Question 11

Complex retroviruses encode

Answer 11

accessory genes 
tat 
rev
nef 
vif 
vpr
vpu

Question 12

what enzymes does GAG encode?

Answer 12

MA
CA
NC

Question 13

MA

Answer 13

matrix protein that lines the envelope

Question 14

CA

Answer 14

capsid protein
protects the core
most abundant

Question 15

NC

Answer 15

Nucleocapsid protein
protects the genome
forms the core

Question 16

Proteins that POL encodes?

Answer 16

RT
IN
PR

Question 17

RT

Answer 17

reverse transcriptase
transcribes RNA genome
has RNAseH activity

Question 18

IN

Answer 18

integrase protein
encoded by pool gene
needed for integration of provirus

Question 19

PR

Answer 19

protease

essential for gag protein cleavage during maturation

Question 20

ENV encodes proteins

Answer 20

SU

TM

Question 21

SU

Answer 21

surface glycoprotein
outer envelop glycoprotein
major virus antigen

Question 22

TM

Answer 22

Transmembrane Protein

inner component of mature envelope glycoprotein

Question 23

TAT

Answer 23

transactivator

positive regulator of transcription

Question 24

REV

Answer 24

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

Question 25

VIF

Answer 25

viral infectivity | affects particle infectivity

Question 26

VPR

Answer 26

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

Question 27

VPU

Answer 27

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

Question 28

NEF

Answer 28

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

Question 29

steps of Retrovirus replication - 7 steps

Answer 29

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

Question 30

HTLV-1 clinical manifestations - Myelopathies

Answer 30

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

Question 31

HTLV-1 clinical manifestations - Motor disorders

Answer 31

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

Question 32

HTLV-1 clinical manifestations Adult T cell leukemia/lymphoma

Answer 32

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

Question 33

HTLV-1 clinical manifestation in childern

Answer 33

Infective dermatitis is chronic relapsing syndrome

Question 34

HTLV-2 clinical manifestations

Answer 34

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

Question 35

HIV-1 classification

Answer 35

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

Question 36

Group M HIV-1

Answer 36

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

Question 37

HIV-2

Answer 37

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

Question 38

HIV infects cells that carry the receptor and co receptors

Answer 38

CD4 CCR5 CXCR4

Question 39

CD4 expressed on

Answer 39

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

Question 40

CCr5 expressed on

Answer 40

CD4+ T lymphocytes and on macrophages

Question 41

CXCR4 expressed on

Answer 41

CD4+ T lymphocytes and T cell lines

Question 42

M-Tropic

Answer 42

R5 viruses Macrophage tropic infects Macrophage and CD4+ T lymphocyte

Question 43

T-Tropic

Answer 43

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

Question 44

Risk assessment screening guideline

Answer 44

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

Question 45

Behavioral Risk Factor Screening guidelines

Answer 45

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

Question 46

Screening in general is performed for these groups

Answer 46

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

Question 47

what are some lab diagnostic tests for HIV?

Answer 47

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)

Question 48

Lab diagnosis test for Post diagnosis

Answer 48

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

Question 49

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

Answer 49

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

Question 50

During acute infections, pts will develop

Answer 50

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

Question 51

How is acute HIV diagnosed?

Answer 51

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

Question 52

Steps of HIV binding

Answer 52

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

Question 53

What are the 3 structural genes?

Answer 53

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

Question 54

What are the 2 regulatory proteins?

Answer 54

TAT | REV

Question 55

what are the 4 accessory proteins?

Answer 55

VIF VPR VPU NEF