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Journal of Virology, September 2008, p. 8422-8430, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00535-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genetic Characterization of Human Immunodeficiency Virus Type 1 in Elite Controllers: Lack of Gross Genetic Defects or Common Amino Acid Changes{triangledown}

Toshiyuki Miura,1,2,3 Mark A. Brockman,1,2 Chanson J. Brumme,1 Zabrina L. Brumme,1,2 Jonathan M. Carlson,4,5 Florencia Pereyra,1,2 Alicja Trocha,1,3 Marylyn M. Addo,1,2 Brian L. Block,1 Alissa C. Rothchild,1 Brett M. Baker,1 Theresa Flynn,1 Arne Schneidewind,1,2 Bin Li,1,2 Yaoyu E. Wang,1,2 David Heckerman,4 Todd M. Allen,1,2 and Bruce D. Walker1,2,3*

Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129,1 Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,2 Howard Hughes Medical Institute, Chevy Chase, Maryland 20815,3 Microsoft Research, Redmond, Washington 98052,4 Department of Computer Science and Engineering, University of Washington, Seattle, Washington5

Received 10 March 2008/ Accepted 10 June 2008

Despite reports of viral genetic defects in persons who control human immunodeficiency virus type 1 (HIV-1) in the absence of antiviral therapy, the extent to which such defects contribute to the long-term containment of viremia is not known. Most previous studies examining for such defects have involved small numbers of subjects, primarily focused on subjects expressing HLA-B57, or have examined single viral genes, and they have focused on cellular proviral DNA rather than plasma viral RNA sequences. Here, we attempted viral sequencing from 95 HIV-1 elite controllers (EC) who maintained plasma viral loads of <50 RNA copies/ml in the absence of therapy, the majority of whom did not express HLA-B57. HIV-1 gene fragments were obtained from 94% (89/95) of the EC, and plasma viral sequences were obtained from 78% (61/78), the latter indicating the presence of replicating virus in the majority of EC. Of 63 persons for whom nef was sequenced, only three cases of nef deletions were identified, and gross genetic defects were rarely observed in other HIV-1 coding genes. In a codon-by-codon comparison between EC and persons with progressive infection, correcting for HLA bias and coevolving secondary mutations, a significant difference was observed at only three codons in Gag, all three of which represented the historic population consensus amino acid at the time of infection. These results indicate that the spontaneous control of HIV replication is not attributable to shared viral genetic defects or shared viral polymorphisms.

* Corresponding author. Mailing address: Partners AIDS Research Center, Massachusetts General Hospital, 149 13th St., Room 5212 Charlestown, MA 02129. Phone: (617) 724-8332. Fax: (617) 726-4691. E-mail: bwalker{at}partners.org

{triangledown} Published ahead of print on 18 June 2008.

Journal of Virology, September 2008, p. 8422-8430, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00535-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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