BASIC BIOLOGY OF HIV
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Transcript of BASIC BIOLOGY OF HIV
MILESTONES IN DISCOVERY OF HIV
1981-Michael Gottleib
“GRID”
1982-AIDS
1983- LucMontagnier and Francoise Barre Sinoussi
“LAV”
1984- Robert Gallo ( National Institute of Health USA)
“HTLV III”
1986- HIV 2
HIV
Family - Retroviridae
Sub family – Lentivirinae
Group – Lentivirus – HIV 1 & 2
SIV
FIV
Visna maedi virus
Equine infectious anaemia virus
ORIGIN OF HIV
HIV 1 – Closely related to SIV cpz Isolated from Pan troglodytes troglodytes
HIV 2 – SIV sm Sooty mangabey monkey
STRUCTURE OF HIV
• Spherical ,enveloped virus
90- 120 nm
• Nulceocapsid Icosahedral shell Inner core
• Envelope
• Diploid genome
NUCLEOPROTEIN CORE
RNA
Nulceocapsid protein ( NC/P9 )
Basic ProteinPhosphorylated on serine residuesViral assembly
Capsid protein ( CA)Icosahedral viral coreHydrophobic
Enzymes- RT, Protease, Integrase
VIRAL GENES
Structural genes – gag , pol, env
Regulatory genes – tat, rev, nef
Accessory genes- vpu ( vpx in HIV2), vpr, vif
STRUCTURAL GENES
Gag- core and shell of virus
P55 – p15, p18, p24
Env – gp160- gp120, gp41
Pol - RT, Ribonuclease, integrase and protease
REGULATORY GENES
Tat- Trans activator of transcription
Hastens viral protein production
Up regulates rev, nef
Nef- Negative regulation factor
Down regulation of CD4
Rev-Regulator of expression
ACCESORY GENES
Vpr- Transcriptional activator
Promoter region of the virus
Vpu- Suppress CD4 / env interaction
Vif- Virion infectivity factor
Increases infectivity
Increases cell to cell transmission
RECEPTORS & CORECEPTORS
CD 4 - 55 kDa proteinCD4 expressing cells
CD4 + T lymphocytesB lymphocytesMonocytesMacrophagesGlial cells and microglial cells
C types lectin receptorFollicular dendritic cellsDC-SIGN
Coreceptors – CXCR4, CCR5
DIVERSITY OF HIV
HIV 1 – M, N, O, P
Group M ( Major)- 9 subtypes or clades
A, B, C, D, F, G, H, K and CRFs
Group O ( Outlier)- rare
Cameroon, Gabon & France
Group N - Cameroon
Group P- Related to gorilla SIV
World wide - subtype C
USA , Europe – subtype B
Sub Saharan Africa – Subtype C
Asia – CRF 01AE, Subtype C&B
India – Subtype C
REPLICATION CYCLE OF HIV
Binding of gp120 with CD4
Conformational change in gp 120
Fusion with host cell membrane via gp 41
Pre integration complex in cytoplasm of target cell
Reverse transcription of the genomic RNA
Proviral DNA
Integration into host cell chromosome by integrase
Latent phase
Transcription into m RNA
Translation into viral proteins
Assembly of genomic RNA, enzymes, proteins
Budding of progeny virion at lipid rafts
Proteases cleave gag pol precursor
Mature virion
Sexual transmission 0.1- 1%
Blood and blood products >90%
Tissue organ donation 50- 90%
Injection and needle stick injury
0.5-1%
Mother to baby 30%
ROUTES OF TRANSMISSION
RESISTANCE
Thermo labile
Survive in dried blood @ room temperature for 7 days
Inactivated by 50% ethanol 0.5% Lysol
0.5% Paraformaldehyde
0.3% H2O2 10% Household bleach
Surface decontamination- Hypochlorite solution 0.5%
35.3 million [32.2 million – 38.8 million] 32.1 million [29.1 million – 35.3 million]17.7 million [16.4 million – 19.3 million] 3.3 million [3.0 million – 3.7 million]
2.3 million [1.9 million – 2.7 million]2.0 million [1.7 million – 2.4 million]
260 000 [230 000 – 320 000]
1.6 million [1.4 million – 1.9 million]1.4 million [1.2 million – 1.7 million]
210 000 [190 000 – 250 000]
Number of people living with HIV
People newly infected with HIV in 2012
AIDS deaths in 2012
TotalAdults
WomenChildren (<15 years)
TotalAdults
Children (<15 years)
TotalAdults
Children (<15 years)
Global summary of the AIDS epidemic 2012
About 6,300 new HIV infections a day in 2012
About 95% are in low- and middle-income countries
About 700 are in children under 15 years of age
About 5,500 are in adults aged 15 years and older, of whom: ─almost 47% are among women
─about 39% are among young people (15-24)