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Journal of Virology, December 2009, p. 12636-12642, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01236-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Clade-Specific Evolution Mediated by HLA-B*57/5801 in Human Immunodeficiency Virus Type 1 Clade A1 p24{triangledown}

Lyle R. McKinnon,1,2* Rupert Capina,3 Harold Peters,3 Mark Mendoza,3 Joshua Kimani,1,2 Charles Wachihi,2 Anthony Kariri,2 Makobu Kimani,2 Meika Richmond,1 Sandy Koesters Kiazyk,4 Keith R. Fowke,1,2 Walter Jaoko,2 Ma Luo,3 T. Blake Ball,1,2,4,5 and Francis A. Plummer1,2,3,4

Departments of Medical Microbiology,1 Immunolgy, University of Manitoba, Winnipeg, Canada,5 Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya,2 National Microbiology Lab, Public Health Agency of Canada, Winnipeg, Canada,3 National Laboratory for HIV Immunology, Public Health Agency of Canada, Winnipeg, Canada4

Received 15 June 2009/ Accepted 8 September 2009

HLA-B*57-mediated selection pressure leads to a typical escape pathway in human immunodeficiency virus type 1 (HIV-1) CD8 epitopes such as TW10. Whether this T242N pathway is shared by all clades remains unknown. We therefore assessed the nature of HLA-B*57 selection in a large, observational Kenyan cohort where clades A1 and D predominate. While T242N was ubiquitous in clade D HLA-B*57+ subjects, this mutation was rare (15%) in clade A1. Instead, P243T and I247L were selected by clade A1-infected HLA-B*57 subjects but not by HLA-B*5801+ subjects. Our data suggest that clade A1 consensus proline at Gag residue 243 might represent an inherent block to T242N escape in clade A1. We confirmed immunologically that P243T and I247L likely represent escape mutations. HLA-B*57 evolution also differed between clades in the KF11 and IW9 epitopes. A better understanding of clade-specific evolution is important for the development of HIV vaccines in regions with multiple clades.


* Corresponding author. Mailing address: Department of Medical Microbiology, University of Nairobi, P.O. Box 19676-00202, Nairobi, Kenya. Phone: 254-723-430009. Fax: 254-20-272-8860. E-mail: sijuisijali{at}gmail.com

{triangledown} Published ahead of print on 16 September 2009.


Journal of Virology, December 2009, p. 12636-12642, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01236-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.