mechanism of re combination in hiv-1- a review

8/9/2019 Mechanism of Re Combination in HIV-1- A Review

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Mechanism of Recombination in

Human Immunodeficiency Virus Type1 (HIV-1): A Review

Md. Mesbah Uddin

Student ID-050712

14 February 2010


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Introduction

HIV is the etiological agent of AIDS

People living with HIV 33.4 million (till 2008)

New HIV infections 2.7 million (in 2008)

Death due to AIDS 2 million (in 2008)

Total death 25 million (from 1981-2006)

Ultimate control dependent on an effective,preventive vaccine.

Greatest challenge is HIV-1 diversity


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GeneticDiversity of

HIV-1

HIV-1

Group M

A

B

C

D

F

G

H

J

K

CRF

URF

Group N

Group O

Group P

Subtypes

Recombinant Form

Geog

raphicalDistribution ofHIV-1


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GeneticDiversity in HIV-1

Reverse Transcription

Recombination


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Prerequisite for Recombination

Cells infected by twodistinct types/

subtypes of HIV-1

Copackaging of twodistinct RNA in the

same virion

New cells infectedwith virion withheterodimeric

genomeRecombination


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Emergence ofcirculating recombinant

forms (CRF)

CRF 03_ABCRF06_cpxCRF27_cpx


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Objective

To reviewthe probable mechanisms

underlyingHIV-1 recombination


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In General


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Double stranded proviral DNA Generation


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(-) strandDNA Donor RNA

Acceptor RNA

Free nascentDNA

Annealing ofnascent DNA

with the acceptor

Resumption ofDNAsynthesis

On acceptor template

DNAsynthesis

stoppedon pause site

Pause Driven

Recombination

Minus strand recombination


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Donor RNA

Acceptor RNA

Donor template degradation

& acceptor-nascentDNAdocking

Primer strand

realignment

Recombinant provirus

Resumption ofDNAsynthesis

Acceptor invasion

model

Minus strand recombination


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Acceptor RNADonor RNA

Nascent (-) DNA

Interactive hairpin structure

Stem ofhairpin

Donor-acceptor

interaction

Docking ofnascent DNA

with acceptor RNA

Template switching

Interactive Hairpin model Minus strand recombination


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lhNefsequence

(~300bp)

Complementary sequence

tRNAsequence

HITMEfor minusstrand

PPT


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minusDNAstrand

from twodistinctviralgenome

Stranddisplacement

Assimilation of

plusstrand

Plus strand DNA

recombination:

strand DisplacementAssimilation model


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Summary

HIV-1

Recombination

Minus Strand

recombination

Forced o y

c oicePause driven

RNA structure

drivenrecombination

Acce torinvasion model

InteractiveHair in model

HITME

Plus Strand

Recombination

StrandDis lacement

Assimilation

Model

HITME


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Conclusion

Discussed models are based on data obtained

from in vitro reconstituted systems

The situation in vivo is expected to be more

complex

Further studies are needed to evaluate

existence of these mechanisms in vivo


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Outlook

In vivo study of proposed mechanisms using

CRFs could be the recommendation from this

work, for proper understanding of the biology

of HIV-1 recombination


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mechanism of re combination in hiv-1- a review

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