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Science 16 March 2007:
Vol. 315. no. 5818, pp. 1583 - 1586
DOI: 10.1126/science.1131528
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Reports

Founder Effects in the Assessment of HIV Polymorphisms and HLA Allele Associations

Tanmoy Bhattacharya,1,2 Marcus Daniels,1 David Heckerman,3 Brian Foley,1 Nicole Frahm,4 Carl Kadie,3 Jonathan Carlson,3,5 Karina Yusim,1 Ben McMahon,1 Brian Gaschen,1 Simon Mallal,6 James I. Mullins,7 David C. Nickle,7 Joshua Herbeck,7 Christine Rousseau,7 Gerald H. Learn,7 Toshiyuki Miura,4 Christian Brander,4 Bruce Walker,4,8 Bette Korber1,2*

Escape from T cell–mediated immune responses affects the ongoing evolution of rapidly evolving viruses such as HIV. By applying statistical approaches that account for phylogenetic relationships among viral sequences, we show that viral lineage effects rather than immune escape often explain apparent human leukocyte antigen (HLA)–mediated immune-escape mutations defined by older analysis methods. Phylogenetically informed methods identified immune-susceptible locations with greatly improved accuracy, and the associations we identified with these methods were experimentally validated. This approach has practical implications for understanding the impact of host immunity on pathogen evolution and for defining relevant variants for inclusion in vaccine antigens.

1 Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
2 Santa Fe Institute, Santa Fe, NM 87501, USA.
3 Machine Learning and Applied Statistics Group, Microsoft Research, Redmond, WA 98052, USA.
4 Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
5 Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.
6 Center for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital, Perth, Australia.
7 Department of Microbiology, University of Washington, Seattle, WA 98195–8070, USA.
8 Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

* To whom correspondence should be addressed. E-mail: btk{at}lanl.gov

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Science. ISSN 0036-8075 (print), 1095-9203 (online)