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Journal of Virology, July 2006, p. 7226-7234, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.02014-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts

A. J. Frater,^1, C. T. T. Edwards,^1, N. McCarthy,² J. Fox,³ H. Brown,¹ A. Milicic,¹ N. Mackie,³ T. Pillay,¹ J. W. Drijfhout,⁴ S. Dustan,³ J. R. Clarke,³ E. C. Holmes,² H. T. Zhang,¹ K. Pfafferott,¹ P. J. Goulder,¹ M. O. McClure,³ J. Weber,³ R. E. Phillips,^1* and S. Fidler³

The James Martin 21st Century School, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom,¹ Department of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom,² Division of Medicine, Wright Fleming Institute, Imperial College, St. Mary's Hospital, 4th Floor, Norfolk Place, Paddington, London W2 1PG, United Kingdom,³ Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands⁴

Received 21 September 2005/ Accepted 5 April 2006

Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.

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

A.J.F. and C.T.T.E. contributed equally to this work.

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