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Journal of Virology, April 2007, p. 3369-3376, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.01295-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Frequent Intrapatient Recombination between Human Immunodeficiency Virus Type 1 R5 and X4 Envelopes: Implications for Coreceptor Switch{triangledown}

Mattias Mild,1,2 Joakim Esbjörnsson,1,2 Eva Maria Fenyö,2 and Patrik Medstrand1*

Department of Experimental Medical Science, Lund University, BMC B13, 221 84 Lund, Sweden,1 Department of Laboratory Medicine, Division of Medical Microbiology/Virology, Lund University, Sölvegatan 23, 22362 Lund, Sweden2

Received 20 June 2006/ Accepted 12 January 2007

Emergence of human immunodeficiency virus type 1 (HIV-1) populations that switch or broaden coreceptor usage from CCR5 to CXCR4 is intimately coupled to CD4+ cell depletion and disease progression toward AIDS. To better understand the molecular mechanisms involved in the coreceptor switch, we determined the nucleotide sequences of 253 V1 to V3 env clones from 27 sequential HIV-1 subtype B isolates from four patients with virus populations that switch coreceptor usage. Coreceptor usage of clones from dualtropic R5X4 isolates was characterized experimentally. Sequence analysis revealed that 9% of the clones from CXCR4-using isolates had originated by recombination events between R5 and X4 viruses. The majority (73%) of the recombinants used CXCR4. Furthermore, coreceptor usage of the recombinants was determined by a small region of the envelope, including V3. This is the first report demonstrating that intrapatient recombination between viruses with distinct coreceptor usage occurs frequently. It has been proposed that X4 viruses are more easily suppressed by the immune system than R5 viruses. We hypothesize that recombination between circulating R5 viruses and X4 viruses can result in chimeric viruses with the potential to both evade the immune system and infect CXCR4-expressing cells. The broadening in cell tropism of the viral population to include CXCR4-expressing cells would gradually impair the immune system and eventually allow the X4 population to expand. In conclusion, intrapatient recombination between viruses with distinct coreceptor usage may contribute to the emergence of X4 viruses in later stages of infection.

* Corresponding author. Mailing address: Department of Experimental Medical Science, Lund University, BMC B13, 221 84 Lund, Sweden. Phone: 46-46-2221489. Fax: 46-46-2220899. E-mail: patrik.medstrand{at}med.lu.se.

{triangledown} Published ahead of print on 24 January 2007.

Journal of Virology, April 2007, p. 3369-3376, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.01295-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Ince, W. L., Harrington, P. R., Schnell, G. L., Patel-Chhabra, M., Burch, C. L., Menezes, P., Price, R. W., Eron, J. J. Jr., Swanstrom, R. I. (2009). Major Coexisting Human Immunodeficiency Virus Type 1 env Gene Subpopulations in the Peripheral Blood Are Produced by Cells with Similar Turnover Rates and Show Little Evidence of Genetic Compartmentalization. J. Virol. 83: 4068-4080 [Abstract] [Full Text]  


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