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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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