Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination.

Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Research Abstract Details 

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Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Abstract Text:

Heather A Baird,Yong Gao, Galetto,Matthew Lalonde,Reshma M Anthony, Giacomoni,Measho Abreha,Jeffrey J Destefano,Matteo Negroni,Eric J Arts,

BACKGROUND: HIV-1 recombination between different subtypes has a major impact on the global epidemic. The generation of these intersubtype recombinants follows a defined set of events starting with dual infection of a host cell, heterodiploid virus production, strand transfers during reverse transcription, and then selection. In this study, recombination frequencies were measured in the C1-C4 regions of the envelope gene in the presence (using a multiple cycle infection system) and absence (in vitro reverse transcription and single cycle infection systems) of selection for replication-competent virus. Ugandan subtypes A and D HIV-1 env sequences (115-A, 120-A, 89-D, 122-D, 126-D) were employed in all three assay systems. These subtypes co-circulate in East Africa and frequently recombine in this human population. RESULTS: Increased sequence identity between viruses or RNA templates resulted in increased recombination frequencies, with the exception of the 115-A virus or RNA template. Analyses of the recombination breakpoints and mechanistic studies revealed that the presence of a recombination hotspot in the C3/V4 env region, unique to 115-A as donor RNA, could account for the higher recombination frequencies with the 115-A virus/template. Single-cycle infections supported proportionally less recombination than the in vitro reverse transcription assay but both systems still had significantly higher recombination frequencies than observed in the multiple-cycle virus replication system. In the multiple cycle assay, increased replicative fitness of one HIV-1 over the other in a dual infection dramatically decreased recombination frequencies. CONCLUSION: Sequence variation at specific sites between HIV-1 isolates can introduce unique recombination hotspots, which increase recombination frequencies and skew the general observation that decreased HIV-1 sequence identity reduces recombination rates. These findings also suggest that the majority of intra- or intersubtype A/D HIV-1 recombinants, generated with each round of infection, are not replication-competent and do not survive in the multiple-cycle system. Ability of one HIV-1 isolate to outgrow the other leads to reduced co-infections, heterozygous virus production, and recombination frequencies.

Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Publishing Authors By Initials

HA Baird,Y Gao,R Galetto,M Lalonde,RM Anthony,V Giacomoni,M Abreha,JJ Destefano,M Negroni,EJ Arts,

For similar biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: viral physiology: virus replication research abstracts see: biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: viral physiology: virus replication research

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Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Retrovirology

VOLUME: 3

Page Numbers: 91

Journal Abbreviation: Retrovirology

ISSN: 1742-4690

DAY: 12

MONTH: 12

YEAR: 2006

Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101216893

Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Keywords Mesh Terms:

KEYWORDS: Virus Replication

MESH TERMS: chemistry

Chemical & Substance for Abstract: Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Information

Substance Name: RNA, Viral

Registry Number: 0

Grant and Affiliation Information for Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination.

AFFILIATION: Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. heather_baird@dhiusa.com

Country: England

AGENCY: United States NIGMS

GRANT: GM051140

ACRONYM: GM

MEDLINETA: Retrovirology

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