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Journal of Virology, September 2005, p. 11981-11989, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11981-11989.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Molecular Footprint of Drug-Selective Pressure in a Human Immunodeficiency Virus Transmission Chain{dagger}

Philippe Lemey,1,2* Inge Derdelinckx,2 Andrew Rambaut,1 Kristel Van Laethem,2 Stephanie Dumont,2 Steve Vermeulen,2 Eric Van Wijngaerden,3 and Anne-Mieke Vandamme2

Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom,1 Rega Institute for Medical Research, KULeuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium,2 University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium3

Received 17 March 2005/ Accepted 23 June 2005

Known human immunodeficiency virus (HIV) transmission histories are invaluable models for investigating the evolutionary and transmission dynamics of the virus and to assess the accuracy of phylogenetic reconstructions. Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. Phylogenetic analyses in pol using likelihood methods inferred an evolutionary history not fully compatible with the known transmission history. This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. On the other hand, a fully compatible phylogenetic tree was reconstructed from the env sequences. We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. An increased fixation rate of mutations in the HIV population of the multidrug-resistant patient was demonstrated using molecular clock modeling. We show that molecular evolutionary analyses, guided by a known transmission history, can reveal the presence of confounding factors like natural selection and caution should be taken when accurate descriptions of HIV evolution are required.

* Corresponding author. Present address: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Phone: 44 1865 271272. Fax: 44 1865 271249. E-mail: philippe.lemey{at}zoo.ox.ac.uk.

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

Journal of Virology, September 2005, p. 11981-11989, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11981-11989.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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