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Journal of Virology, May 2002, p. 5278-5284, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5278-5284.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Molecular Evolution of Human Immunodeficiency Virus env in Humans and Monkeys: Similar Patterns Occur during Natural Disease Progression or Rapid Virus Passage

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute,¹ Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115,² Division of Newborn Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111,³ Center for AIDS Research, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710,⁴ Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322⁵

Received 11 October 2001/ Accepted 12 February 2002

Neonatal rhesus macaque 95-3 was inoculated with nonpassaged simian-human immunodeficiency virus strain SHIV-vpu⁺, which encodes env of the laboratory-adapted human immunodeficiency virus (HIV) strain IIIB and is considered nonpathogenic. CD4⁺ T-cell counts dropped to <200 cells/µl within 4.6 years, and monkey 95-3 died with opportunistic infections 5.9 years postinoculation. Transfer of blood from 95-3 to two naive adult macaques resulted in high peak viral loads and rapid, persistent T-cell depletion. Progeny virus evolved in 95-3 despite high SHIV-vpu⁺ neutralizing antibody titers and still used CXCR4 but, in contrast to parental SHIV-vpu⁺, productively infected macrophages and resisted neutralization. Sequence analysis revealed three new potential glycosylation sites in gp120; another two were lost. Strikingly similar mutations were detected in a laboratory worker who progressed to AIDS after accidental HIV-IIIB infection (T. Beaumont et al., J. Virol. 75:2246-2252, 2001), thus supporting the SHIV-vpu⁺/rhesus macaque system as a relevant model. Similar mutations were also described after rapid passage of chimeric viruses encoding IIIB env in rhesus and pig-tailed macaques (M. Cayabyab et al., J. Virol. 73:976-984, 1999; Z. Q. Liu et al., Virology 260:295-307, 1999; S. V. Narayan et al., Virology 256:54-63, 1999; R. Raghavan et al., Brain Pathol. 7:851-861, 1997; E. B. Stephens et al., Virology 231:313-321, 1997). Thus, HIV-IIIB env evolved similarly in three different species; this selection occurred in chronically infected individuals during disease progression as well as after rapid virus passage. We postulate that evolutionary pressure led to the outgrowth of more aggressive viral variants in all three species.

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