HIV - retroviruses Flashcards

0
Q

Pneumocystis Carinii Pneumonia

A

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

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1
Q

Kaposi’s Sarcoma

A

relatively benign cancer usually seen in elderly

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

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2
Q

AIDS defined by CDC in

A

september of 1982

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3
Q

1983

A

science realized that HIV-1 is causative agent of AIDS

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4
Q

retroviruses

A

enveloped
+ssRNA
that replicate through DNA intermediate using reverse transcriptase

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5
Q

Deltaretrovirus

A

complex
Oncovirinae
causes Human T cell leukemia

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6
Q

Lentivirus

A

complex
Lentivirinae
HIV-1, HIV-2, FIV

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7
Q

retroviruses encode

A

RNA dependent DNA pol transcriptase

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8
Q

Retroviruses replicate through

A

a DNA intermediate termed Provirus

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9
Q

How is provirus integrated into the host genome?

A

with help of integrase

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10
Q

What genes do simple retroviruses encode?

A

gag
pol
env

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11
Q

Complex retroviruses encode

A
accessory genes 
tat 
rev
nef 
vif 
vpr
vpu
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12
Q

what enzymes does GAG encode?

A

MA
CA
NC

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13
Q

MA

A

matrix protein that lines the envelope

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14
Q

CA

A

capsid protein
protects the core
most abundant

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15
Q

NC

A

Nucleocapsid protein
protects the genome
forms the core

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16
Q

Proteins that POL encodes?

A

RT
IN
PR

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17
Q

RT

A

reverse transcriptase
transcribes RNA genome
has RNAseH activity

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18
Q

IN

A

integrase protein
encoded by pool gene
needed for integration of provirus

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19
Q

PR

A

protease

essential for gag protein cleavage during maturation

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20
Q

ENV encodes proteins

A

SU

TM

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21
Q

SU

A

surface glycoprotein
outer envelop glycoprotein
major virus antigen

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22
Q

TM

A

Transmembrane Protein

inner component of mature envelope glycoprotein

23
Q

TAT

A

transactivator

positive regulator of transcription

24
Q

REV

A

regulation of viral expression

allows export of unspliced and partially spliced transcripts from nucleus

25
Q

VIF

A

viral infectivity

affects particle infectivity

26
Q

VPR

A

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

27
Q

VPU

A

viral protein U

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

28
Q

NEF

A

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

29
Q

steps of Retrovirus replication - 7 steps

A

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

30
Q

HTLV-1 clinical manifestations - Myelopathies

A
Tropical spastic paraparesis 
Inflammation, spinal cord atrophy 
affects age 30-50, slow development 
leg weakness 
Hyperreflexia 
Urinary and fecal incontinence
31
Q

HTLV-1 clinical manifestations - Motor disorders

A

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

32
Q

HTLV-1 clinical manifestations Adult T cell leukemia/lymphoma

A

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

33
Q

HTLV-1 clinical manifestation in childern

A

Infective dermatitis is chronic relapsing syndrome

34
Q

HTLV-2 clinical manifestations

A

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

35
Q

HIV-1 classification

A

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

36
Q

Group M HIV-1

A

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

37
Q

HIV-2

A

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

38
Q

HIV infects cells that carry the receptor and co receptors

A

CD4
CCR5
CXCR4

39
Q

CD4 expressed on

A

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

40
Q

CCr5 expressed on

A

CD4+ T lymphocytes and on macrophages

41
Q

CXCR4 expressed on

A

CD4+ T lymphocytes and T cell lines

42
Q

M-Tropic

A

R5 viruses
Macrophage tropic
infects Macrophage and CD4+ T lymphocyte

43
Q

T-Tropic

A

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

44
Q

Risk assessment screening guideline

A

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

45
Q

Behavioral Risk Factor Screening guidelines

A

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

46
Q

Screening in general is performed for these groups

A

all patients aged 13-64 years

All pts initiating treatment for TB should be screened routinely for HIV infection

47
Q

what are some lab diagnostic tests for HIV?

A

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)

48
Q

Lab diagnosis test for Post diagnosis

A

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

49
Q

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

A

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

50
Q

During acute infections, pts will develop

A
non specifc viral illness 
lymphadenopathy 
fever 
fatigue 
rash 
that usually lasts about 1-2 weeks
51
Q

How is acute HIV diagnosed?

A

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

52
Q

Steps of HIV binding

A
  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
53
Q

What are the 3 structural genes?

A

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

54
Q

What are the 2 regulatory proteins?

A

TAT

REV

55
Q

what are the 4 accessory proteins?

A

VIF
VPR
VPU
NEF