This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Quiñones-Mateu, M. E.
Right arrow Articles by Arts, E. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Quiñones-Mateu, M. E.
Right arrow Articles by Arts, E. J.

 Previous Article  |  Next Article 

Journal of Virology, October 2002, p. 9600-9613, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9600-9613.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro Intersubtype Recombinants of Human Immunodeficiency Virus Type 1: Comparison to Recent and Circulating In Vivo Recombinant Forms

Miguel E. Quiñones-Mateu,1,{dagger} Yong Gao,1 Sarah C. Ball,1 Andre J. Marozsan,2 Awet Abraha,1 and Eric J. Arts1,2*

Division of Infectious Diseases, Department of Medicine,1 Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 441062

Received 7 March 2002/ Accepted 10 June 2002

The increased prevalence of human immunodeficiency virus type 1 (HIV-1) intersubtype recombinants (ISRs) is shaping HIV-1 evolution throughout the world and will have an impact on both therapeutic and vaccine strategies. This study was designed to generate and compare in vitro ISRs to those isolated from HIV-infected individuals throughout the world. Human peripheral blood mononuclear cells were dually infected with seven pairs of HIV-1 isolates from different subtypes (i.e., A to F). Recombinant crossover sites were mapped to specific regions in the envelope (env) gene by using a cloning-hybridization technique and subtype-specific probes. In vitro intersubtype recombination was at least twofold more frequent in the V1-to-V3 region than in any other env fragment, i.e., C1 to V1, V3 to V5, or V5 to gp41. Sequence and recombination site analyses suggested the C2 env domain as a "hot region" for recombination and selection of replication-competent ISRs during the 15-day incubation. In addition to these regional preferences for env recombination, homopolymeric nucleotide tracts, i.e., sequences known to pause reverse transcriptase and promote template switching, were found in most in vitro crossover sites. ISRs, originating from recent dual infections and limited transmission events, partly retained this in vitro regional or sequence preference for recombination sites. However, a shift to crossover sites flanking the gp120-coding sequence was evident in the stable circulating recombinant forms of HIV-1. Based on these findings, HIV-1 recombinants generated from these dual infections may be used as a model for in vivo intersubtype recombination and for the design of various diagnostic assays and vaccine constructs.

* Corresponding author. Mailing address: Division of Infectious Diseases, BRB 1029, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106. Phone: (216) 368-8904. Fax: (216) 368-2034. E-mail: eja3{at}po.cwru.edu.

{dagger} Present address: Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.

Journal of Virology, October 2002, p. 9600-9613, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9600-9613.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yang, G., Paintsil, E., Dutschman, G. E., Grill, S. P., Wang, C.-J., Wang, J., Tanaka, H., Hamasaki, T., Baba, M., Cheng, Y.-C. (2009). Impact of Novel Human Immunodeficiency Virus Type 1 Reverse Transcriptase Mutations P119S and T165A on 4'-Ethynylthymidine Analog Resistance Profile. Antimicrob. Agents Chemother. 53: 4640-4646 [Abstract] [Full Text]  
  • Onafuwa-Nuga, A., Telesnitsky, A. (2009). The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination. Microbiol. Mol. Biol. Rev. 73: 451-480 [Abstract] [Full Text]  
  • Baird, H. A., Galetto, R., Gao, Y., Simon-Loriere, E., Abreha, M., Archer, J., Fan, J., Robertson, D. L., Arts, E. J., Negroni, M. (2006). Sequence determinants of breakpoint location during HIV-1 intersubtype recombination. Nucleic Acids Res 0: gkl669v3-14 [Abstract] [Full Text]  
  • Galetto, R., Giacomoni, V., Veron, M., Negroni, M. (2006). Dissection of a Circumscribed Recombination Hot Spot in HIV-1 after a Single Infectious Cycle. J. Biol. Chem. 281: 2711-2720 [Abstract] [Full Text]  
  • Troyer, R. M., Collins, K. R., Abraha, A., Fraundorf, E., Moore, D. M., Krizan, R. W., Toossi, Z., Colebunders, R. L., Jensen, M. A., Mullins, J. I., Vanham, G., Arts, E. J. (2005). Changes in Human Immunodeficiency Virus Type 1 Fitness and Genetic Diversity during Disease Progression. J. Virol. 79: 9006-9018 [Abstract] [Full Text]  
  • Chen, J., Rhodes, T. D., Hu, W.-S. (2005). Comparison of the Genetic Recombination Rates of Human Immunodeficiency Virus Type 1 in Macrophages and T Cells. J. Virol. 79: 9337-9340 [Abstract] [Full Text]  
  • Chin, M. P. S., Rhodes, T. D., Chen, J., Fu, W., Hu, W.-S. (2005). Identification of a major restriction in HIV-1 intersubtype recombination. Proc. Natl. Acad. Sci. USA 102: 9002-9007 [Abstract] [Full Text]  
  • Lanciault, C., Champoux, J. J. (2005). Effects of Unpaired Nucleotides within HIV-1 Genomic Secondary Structures on Pausing and Strand Transfer. J. Biol. Chem. 280: 2413-2423 [Abstract] [Full Text]  
  • Flynn, J. A., An, W., King, S. R., Telesnitsky, A. (2004). Nonrandom Dimerization of Murine Leukemia Virus Genomic RNAs. J. Virol. 78: 12129-12139 [Abstract] [Full Text]  
  • Derebail, S. S., DeStefano, J. J. (2004). Mechanistic Analysis of Pause Site-dependent and -independent Recombinogenic Strand Transfer from Structurally Diverse Regions of the HIV Genome. J. Biol. Chem. 279: 47446-47454 [Abstract] [Full Text]  
  • Marozsan, A. J., Fraundorf, E., Abraha, A., Baird, H., Moore, D., Troyer, R., Nankja, I., Arts, E. J. (2004). Relationships between Infectious Titer, Capsid Protein Levels, and Reverse Transcriptase Activities of Diverse Human Immunodeficiency Virus Type 1 Isolates. J. Virol. 78: 11130-11141 [Abstract] [Full Text]  
  • Galetto, R., Moumen, A., Giacomoni, V., Veron, M., Charneau, P., Negroni, M. (2004). The Structure of HIV-1 Genomic RNA in the gp120 Gene Determines a Recombination Hot Spot in Vivo. J. Biol. Chem. 279: 36625-36632 [Abstract] [Full Text]  
  • Kapoor, A., Jones, M., Shafer, R. W., Rhee, S.-Y., Kazanjian, P., Delwart, E. L. (2004). Sequencing-Based Detection of Low-Frequency Human Immunodeficiency Virus Type 1 Drug-Resistant Mutants by an RNA/DNA Heteroduplex Generator-Tracking Assay. J. Virol. 78: 7112-7123 [Abstract] [Full Text]  
  • An, W., Telesnitsky, A. (2004). Human Immunodeficiency Virus Type 1 Transductive Recombination Can Occur Frequently and in Proportion to Polyadenylation Signal Readthrough. J. Virol. 78: 3419-3428 [Abstract] [Full Text]  
  • Collins, J. A., Thompson, M. G., Paintsil, E., Ricketts, M., Gedzior, J., Alexander, L. (2004). Competitive Fitness of Nevirapine-Resistant Human Immunodeficiency Virus Type 1 Mutants. J. Virol. 78: 603-611 [Abstract] [Full Text]  
  • Rhodes, T., Wargo, H., Hu, W.-S. (2003). High Rates of Human Immunodeficiency Virus Type 1 Recombination: Near-Random Segregation of Markers One Kilobase Apart in One Round of Viral Replication. J. Virol. 77: 11193-11200 [Abstract] [Full Text]  
  • Moumen, A., Polomack, L., Unge, T., Veron, M., Buc, H., Negroni, M. (2003). Evidence for a Mechanism of Recombination during Reverse Transcription Dependent on the Structure of the Acceptor RNA. J. Biol. Chem. 278: 15973-15982 [Abstract] [Full Text]  
  • Balakrishnan, M., Roques, B. P., Fay, P. J., Bambara, R. A. (2003). Template Dimerization Promotes an Acceptor Invasion-Induced Transfer Mechanism during Human Immunodeficiency Virus Type 1 Minus-Strand Synthesis. J. Virol. 77: 4710-4721 [Abstract] [Full Text]  
  • Ball, S. C., Abraha, A., Collins, K. R., Marozsan, A. J., Baird, H., Quinones-Mateu, M. E., Penn-Nicholson, A., Murray, M., Richard, N., Lobritz, M., Zimmerman, P. A., Kawamura, T., Blauvelt, A., Arts, E. J. (2002). Comparing the Ex Vivo Fitness of CCR5-Tropic Human Immunodeficiency Virus Type 1 Isolates of Subtypes B and C. J. Virol. 77: 1021-1038 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»