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Journal of Virology, April 2009, p. 3556-3567, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02132-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Quantitating the Multiplicity of Infection with Human Immunodeficiency Virus Type 1 Subtype C Reveals a Non-Poisson Distribution of Transmitted Variants ^,

M.-R. Abrahams,¹ J. A. Anderson,² E. E. Giorgi,^3,4 C. Seoighe,¹ K. Mlisana,⁵ L.-H. Ping,² G. S. Athreya,³ F. K. Treurnicht,¹ B. F. Keele,⁶ N. Wood,¹ J. F. Salazar-Gonzalez,⁶ T. Bhattacharya,^3,7 H. Chu,² I. Hoffman,² S. Galvin,² C. Mapanje,⁸ P. Kazembe,⁸ R. Thebus,¹ S. Fiscus,² W. Hide,⁹ M. S. Cohen,² S. Abdool Karim,⁵ B. F. Haynes,¹⁰ G. M. Shaw,⁶ B. H. Hahn,⁶ B. T. Korber,^3,7 R. Swanstrom,² C. Williamson,^1* for the CAPRISA Acute Infection Study Team and the Center for HIV-AIDS Vaccine Immunology Consortium

Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa,¹ University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,² Los Alamos National Laboratory, Los Alamos, New Mexico,³ University of Massachusetts, Amherst, Massachusetts,⁴ Centre for the AIDS Programme of Research in South Africa, University of Kwa-Zulu Natal, Durban, South Africa,⁵ University of Alabama at Birmingham, Birmingham, Alabama,⁶ Santa Fe Institute, Santa Fe, New Mexico,⁷ Kamuzu Central Hospital, Lilongwe, Malawi,⁸ South African Bioinformatics Institute, University of Western Cape, Cape Town, South Africa,⁹ Duke University Medical Center, Durham, North Carolina,¹⁰

Received 9 October 2008/ Accepted 24 December 2008

Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.

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* Corresponding author. Mailing address: Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South Africa. Phone: 27-21-406 6683. Fax: 27-21-406 6682. E-mail: carolyn.williamson{at}uct.ac.za

Published ahead of print on 4 February 2009.

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

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Journal of Virology, April 2009, p. 3556-3567, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02132-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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