BASIC BIOLOGY OF HIV

BASIC BIOLOGY OF HIVDr Swathy Lekshmi j l

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

1986- First Report of HIV Infection from India

Dr Suniti Solmon

First AIDS patient from Mumbai

1970- Reverse Transcriptase enzyme

David Baltimore and Howard

Temin

1985- ELISA

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

ENVELOPE

Lipid Bilayer

gp 120

gp41

Matrix core protein

VIRAL GENES

Structural genes – gag , pol, env

Regulatory genes – tat, rev, nef

Accessory genes- vpu ( vpx in HIV2), vpr, vif

LTR

gagpol

envvif

vpr

nef

tatrev

HIV GENOME

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

HIV 21986- from west Africa

Genome- vpx

Envelope- gp36

Less virulent

Less transmissibility

Greater homology with SIV

Resistance to NNRTI’s

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

Global estimates for adults and children 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)

HIV VACCINE

High mutability

Diverse antigenic types

Long latency

Persistence in infected cells

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