HIV - retroviruses Flashcards
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
Kaposi’s Sarcoma
relatively benign cancer usually seen in elderly
but cases were starting to present in 1981 in young gay men
AIDS defined by CDC in
september of 1982
1983
science realized that HIV-1 is causative agent of AIDS
retroviruses
enveloped
+ssRNA
that replicate through DNA intermediate using reverse transcriptase
Deltaretrovirus
complex
Oncovirinae
causes Human T cell leukemia
Lentivirus
complex
Lentivirinae
HIV-1, HIV-2, FIV
retroviruses encode
RNA dependent DNA pol transcriptase
Retroviruses replicate through
a DNA intermediate termed Provirus
How is provirus integrated into the host genome?
with help of integrase
What genes do simple retroviruses encode?
gag
pol
env
Complex retroviruses encode
accessory genes tat rev nef vif vpr vpu
what enzymes does GAG encode?
MA
CA
NC
MA
matrix protein that lines the envelope
CA
capsid protein
protects the core
most abundant
NC
Nucleocapsid protein
protects the genome
forms the core
Proteins that POL encodes?
RT
IN
PR
RT
reverse transcriptase
transcribes RNA genome
has RNAseH activity
IN
integrase protein
encoded by pool gene
needed for integration of provirus
PR
protease
essential for gag protein cleavage during maturation
ENV encodes proteins
SU
TM
SU
surface glycoprotein
outer envelop glycoprotein
major virus antigen
TM
Transmembrane Protein
inner component of mature envelope glycoprotein
TAT
transactivator
positive regulator of transcription
REV
regulation of viral expression
allows export of unspliced and partially spliced transcripts from nucleus
VIF
viral infectivity
affects particle infectivity
VPR
viral protein R
transport of DNA to nucleus, augments virion production
cell cycle arrest
VPU
viral protein U
promotes intracellular degradation of CD4 and enhances release of virus from cell membrane
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
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
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
HTLV-1 clinical manifestations - Motor disorders
ALS-like symptoms
weakness and muscle fasciculation
affects the anterior gray horn and ventral root nerves
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»_space;T cell proliferation
Lymphadenopathy, rapidly fatal without treatment
HTLV-1 clinical manifestation in childern
Infective dermatitis is chronic relapsing syndrome
HTLV-2 clinical manifestations
associated with atypical T cell hairy Leukemia
Subtype of Chronic Lymphoid Leukemia - abnormal B lymphocytes
-Pancytopenia
-Easy bruising
-Fatigue
HIV-1 classification
Major group - M
Outlier group O
new groups N
new groups P
Group M HIV-1
> 90% of all HIV-1 infections
9 genetically distinct subtypes
A-K
HIV-2
has an extra accessory protein over HIV-1
8 groups: A-H
A and B most common
HIV infects cells that carry the receptor and co receptors
CD4
CCR5
CXCR4
CD4 expressed on
surface of CD4 T lymphocytes (helper T lymphocytes) and macrophages (including dendritic cells)
CCr5 expressed on
CD4+ T lymphocytes and on macrophages
CXCR4 expressed on
CD4+ T lymphocytes and T cell lines
M-Tropic
R5 viruses
Macrophage tropic
infects Macrophage and CD4+ T lymphocyte
T-Tropic
X4 viruses
T cell tropic
infects CD4+ T lymphocytes and CD4+ T cell lymphoblastoid cell line
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
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
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
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)
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
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
During acute infections, pts will develop
non specifc viral illness lymphadenopathy fever fatigue rash that usually lasts about 1-2 weeks
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
Steps of HIV binding
- HIV gp120 binds to T cell CD4
- conformational change in gp120 promotes binding to chemokine receptor
- conformational change in gp41 exposes fusion peptide, which inserts into T cell membrane
- Fusion of viral and cell membranes
What are the 3 structural genes?
ENV - gp120 and gp41
GAG - p55, p40 and p24
POL - reverse transcriptase, protease, integrase
What are the 2 regulatory proteins?
TAT
REV
what are the 4 accessory proteins?
VIF
VPR
VPU
NEF