This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 McCutchan, F. E.
Right arrow Articles by Birx, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCutchan, F. E.
Right arrow Articles by Birx, D. L.

 Previous Article  |  Next Article 

Journal of Virology, September 2005, p. 11693-11704, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11693-11704.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

In-Depth Analysis of a Heterosexually Acquired Human Immunodeficiency Virus Type 1 Superinfection: Evolution, Temporal Fluctuation, and Intercompartment Dynamics from the Seronegative Window Period through 30 Months Postinfection{dagger}

F. E. McCutchan,1* M. Hoelscher,2 S. Tovanabutra,1 S. Piyasirisilp,1 E. Sanders-Buell,1 G. Ramos,1 L. Jagodzinski,1 V. Polonis,1 L. Maboko,3 D. Mmbando,4 O. Hoffmann,2,5 G. Riedner,5 F. von Sonnenburg,2 M. Robb,1 and D. L. Birx1

U.S. Military HIV Research Program, 1600 E. Gude Drive, Rockville, Maryland 20850,1 Department of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians-University, Leopoldstrasse 5, Munich, Germany,2 Mbeya Medical Research Programme, Mbeya, Tanzania,3 Mbeya Regional Medical Office, Ministry of Health, Mbeya, Tanzania,4 London School of Hygiene and Tropical Medicine, 50 Bedford Square, London WC1B 3DP, United Kingdom5

Received 26 January 2005/ Accepted 18 June 2005

Human immunodeficiency virus type 1 (HIV-1) superinfection refers to the acquisition of another strain by an already infected individual. Here we report a comprehensive genetic analysis of an HIV-1 superinfection acquired heterosexually. The infected individual was in a high-risk cohort in Tanzania, was exposed to multiple subtypes, and was systematically evaluated every 3 months with a fluorescent multiregion genotyping assay. The subject was identified in the window period and was first infected with a complex ACD recombinant strain, became superinfected 6 to 9 months later with an AC recombinant, and was monitored for >2.5 years. The plasma viral load exceeded 400,000 copies/ml during the first 9 months of infection but resolved to the set point of 67,000 copies/ml by 3 months after superinfection; the CD4 cell count was 377 cells/µl at 30 months. Viral diversity was evaluated with techniques designed to fully sample the quasispecies, permitting direct observation of the evolution, temporal fluctuation, and intercompartment dynamics of the initial and superinfecting strains and recombinants derived from them. Within 3 months of superinfection, seven different molecular forms were detected in gag and six were detected in env. The proportions of forms fluctuated widely over time in plasma and peripheral blood mononuclear cells, illustrating how challenging the detection of dually infected individuals can be. Strain-specific nested PCR confirmed that the superinfecting strain was not present until the 9 month follow-up. This study further defines the parameters and dynamics of superinfection and will foster appropriate studies and approaches to gain a more complete understanding of risk factors for superinfection and its impact on clinical progression, epidemiology, and vaccine design.

* Corresponding author. Mailing address: U.S. Military HIV Research Program, 1600 E. Gude Drive, Rockville, MD 20850. Phone: (301) 251-5065. Fax: (301) 762-7460. E-mail: fmccutchan{at}hivresearch.org.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2005, p. 11693-11704, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11693-11704.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • O'Rourke, S. M., Schweighardt, B., Scott, W. G., Wrin, T., Fonseca, D. P. A. J., Sinangil, F., Berman, P. W. (2009). Novel Ring Structure in the gp41 Trimer of Human Immunodeficiency Virus Type 1 That Modulates Sensitivity and Resistance to Broadly Neutralizing Antibodies. J. Virol. 83: 7728-7738 [Abstract] [Full Text]  
  • Yeh, W. W., Jaru-ampornpan, P., Nevidomskyte, D., Asmal, M., Rao, S. S., Buzby, A. P., Montefiori, D. C., Korber, B. T., Letvin, N. L. (2009). Partial Protection of Simian Immunodeficiency Virus (SIV)-Infected Rhesus Monkeys against Superinfection with a Heterologous SIV Isolate. J. Virol. 83: 2686-2696 [Abstract] [Full Text]  
  • Blish, C. A., Dogan, O. C., Derby, N. R., Nguyen, M.-A., Chohan, B., Richardson, B. A., Overbaugh, J. (2008). Human Immunodeficiency Virus Type 1 Superinfection Occurs despite Relatively Robust Neutralizing Antibody Responses. J. Virol. 82: 12094-12103 [Abstract] [Full Text]  
  • Salazar-Gonzalez, J. F., Bailes, E., Pham, K. T., Salazar, M. G., Guffey, M. B., Keele, B. F., Derdeyn, C. A., Farmer, P., Hunter, E., Allen, S., Manigart, O., Mulenga, J., Anderson, J. A., Swanstrom, R., Haynes, B. F., Athreya, G. S., Korber, B. T. M., Sharp, P. M., Shaw, G. M., Hahn, B. H. (2008). Deciphering Human Immunodeficiency Virus Type 1 Transmission and Early Envelope Diversification by Single-Genome Amplification and Sequencing. J. Virol. 82: 3952-3970 [Abstract] [Full Text]  
  • Guan, M. (2007). Frequency, Causes, and New Challenges of Indeterminate Results in Western Blot Confirmatory Testing for Antibodies to Human Immunodeficiency Virus. CVI 14: 649-659 [Full Text]  
  • Rousseau, C. M., Learn, G. H., Bhattacharya, T., Nickle, D. C., Heckerman, D., Chetty, S., Brander, C., Goulder, P. J. R., Walker, B. D., Kiepiela, P., Korber, B. T., Mullins, J. I. (2007). Extensive Intrasubtype Recombination in South African Human Immunodeficiency Virus Type 1 Subtype C Infections. J. Virol. 81: 4492-4500 [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»