3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

LOWER RATES OF ADAPTIVE EVOLUTION IN HIV-1 DUAL INFECTIONS COMPARED TO SINGLE INFECTIONS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. MoFo0305

Williamson C.¹, Grobler J.¹, Seoighe C.², Ramjee G.³, Morris L.⁴, Abdool Karim S.S.^5
1Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa, ²National Bioinformatics Node, University of Cape Town, Cape Town, South Africa, ³Medical Research Council, Durban, South Africa, ⁴National Institute for Communicable Diseases, Johannesburg, South Africa, ⁵CAPRISA, University of Kwa-Zulu Natal, Durban, South Africa

INTRODUCTION: HIV-infected individuals who harbour two phylogenetically distinct strains of HIV-1 (dual infection), early in infection, appear to progress more rapidly to disease. The mechanism by which this occurs has not been elucidated. We investigated whether viruses from individuals with dual infection evolved more rapidly than viruses from individuals with single infection, and if so, whether the primary mechanism of diversification was through point mutations or recombination.

METHODS: Sequences from randomly sampled clones, collected over time, were analyzed to compare the rates of adaptation through point mutation between viral populations from individuals with dual infection (n=6) and individuals infected with a single strain (single infection, n=8). Estimates of rates of adaptation were determined using a modified version of the McDonald Kreitman test which was adapted for use with divergent and recombining sequences. Full-length sequences from one dually infected individual were generated.

RESULTS: The rate of adaptation through point mutation was significantly lower in the dual infections compared to single infections: 1.67x10^-4 mutations per month per site rose to high frequency or were fixed in the dual infection through positive selection compared to a rate of 4.48 x10^-4 for the single infections (p=0.03). Recombination was evident in all dually infected individuals. Analysis of near full-length genomes generated from a dually infected participant with rapid disease progression at time points 2, 9 and 17 months post infection suggested evasion of cellular and antibody immune pressure through recombination.

CONCLUSIONS: We hypothesize that the increased viral diversity in dual infection enables recombination to contribute significantly to viral adaptation to immune responses and that this results in a decrease in the rate of adaptation affecting individual point mutations. The ability to undergo major genetic shift in viral populations may help to explain rapid disease progression in individuals with dual infection.

Download PDF of this abstract.

050724
Viral dynamics and fitness | MoFo0305 | C. Williamson
Mechanisms of drug resistance and fitness

Copyright © 2005 - International AIDS Society (IAS). All information and content relating to the abstracts from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2005. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2005. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.