clinical group n biology of hiv infection n by duangrat inthorn n mechanism of reverse transcriptase...

Clinical GroupClinical Group

Biology of HIV infection Biology of HIV infection by Duangrat Inthornby Duangrat Inthorn Mechanism of ReverseMechanism of Reverse Transcriptase InhiTranscriptase Inhi

bitors and Protease Inhibitorsbitors and Protease Inhibitors by Tawitch Suriyoby Tawitch Suriyo Animal Models for HIV Animal Models for HIV by Pornpat Intarasunanontby Pornpat Intarasunanont

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Targeting of the CD4 Binding Site Targeting of the CD4 Binding Site by Tan Swee Huangby Tan Swee Huang

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The Biology of HIV InfectionThe Biology of HIV Infection

Asst. Prof. Dr. Duangrat InthornAsst. Prof. Dr. Duangrat Inthorn

Dept. of Environmental Health SDept. of Environmental Health Science, Faculty of Public Health, cience, Faculty of Public Health,

Mahidol UniversityMahidol University

ScopeScope

Biology of HIV , structure of HIV, Biology of HIV , structure of HIV, genome of HIV, life cycle of HIVgenome of HIV, life cycle of HIV

HIV -1 and related RetrovirusHIV -1 and related Retrovirus How it might be stopped (Drug devHow it might be stopped (Drug dev

elopment)elopment)

Introduction

The virus that cause AIDS (Acquired Immunodeficiency Syndrome, AIDS) is HIV (Human Immunodeficiency Virus, HIV)Homosexual have Pneumocyatis carnii together with herpes simplex, cytomegalovirusand CandidaKaposi’s sarcoma- KS is a few case in healthy person

Structure of HIV

-Outer lipid bilayer coat studded with surface (SU, gp 120)-transmembrane (TM,gp41) glycoprotein complexs-beneath the lipid bilayer are matrix proteins (MA)-the virion consist of internal capsular (CA) andnuclear capsid (NC) proteins which surround the single stranded RNA genome.

HIV virion

- show the components and their genetic source-the matrix (MA), internal capsular (CA), and nuclearcapsid (NC) proteins -produce by the gag region-contain gene products of the pol region- RT, integrase and protease.

The Genome of HIVThe Genome of HIV

HIV genome is 9749 nucleotides about HIV genome is 9749 nucleotides about the same size as any other retrovirus, fthe same size as any other retrovirus, for example Rous sarcoma virus (RSV)or example Rous sarcoma virus (RSV)

But genome of HIV is more complex tBut genome of HIV is more complex than RSV since it has extra open readinhan RSV since it has extra open reading frames that clearly code for small prog frames that clearly code for small proteins.teins.

The Genome of HIVThe Genome of HIV

The HIV genome has The HIV genome has ninenine open reading open reading frames but 15 proteins are made in allframes but 15 proteins are made in all

The The GAG/POLGAG/POL polyprotein and the polyprotein and the ENENVV polyprotein are cleaved into several p polyprotein are cleaved into several proteins:roteins:

GAGGAG is cleaved to: MA (matrix), CA(c is cleaved to: MA (matrix), CA(capsid), NC (nucleocapsid), p6apsid), NC (nucleocapsid), p6

POLPOL is cleaved to: PR(protease), RT(reverse is cleaved to: PR(protease), RT(reverse transcriptase), IN (integrase)transcriptase), IN (integrase)

ENVENV is cleaved to : SU (gp120) and (gp41) is cleaved to : SU (gp120) and (gp41) Of other proteins, three are incorporated into Of other proteins, three are incorporated into

the virus the virus (Vif, Vpr and Nef)(Vif, Vpr and Nef) while three are while three are not found in the mature virus: not found in the mature virus: Tat and rev arTat and rev are regulatory proteinse regulatory proteins and and Vpu indirectly assiVpu indirectly assists in assemblysts in assembly

TAT : Trans-Activator of Transcription

REV: Regulator of Virion protein expression

NEF : Negative Regulatory Factor

VIF : Virion Infectivity FactorVPU : Viral Protein UVPR : Viral Protein R

These genes encode small proteins. Theyoverlap with the structural genes (especially ENV) but are different reading frames.