cad a22 4500 390148040 20181103044323.0 cr unu---uuuuu 161201e200205 xx s 000 0 eng 10.5167/uzh-128335 doi 10.1128/JVI.76.10.5278-5284.2002 doi (ZORA)oai:www.zora.uzh.ch:128335 570 ddc 630 ddc 11967343 pmid Molecular evolution of human immunodeficiency virus env in humans and monkeys: similar patterns occur during natural disease progression or rapid virus passage [Elektronische Daten] [Regina Hofmann-Lehmann, Josef Vlasak, Agnès-Laurence Chenine, Pei-Lin Li, Timothy W Baba, David C Montefiori, Harold M McClure, Daniel C Anderson, Ruth M Ruprecht] openAccess eu-repo 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/microl 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. Department of Farm Animals zora Hofmann-Lehmann Regina joint author Vlasak Josef joint author Chenine Agnès-Laurence joint author Li Pei-Lin joint author Baba Timothy W. joint author Montefiori David C. joint author McClure Harold M. joint author Anderson Daniel C. joint author Ruprecht Ruth M. joint author Journal of Virology 76(10):5278-5284 https://www.zora.uzh.ch/id/eprint/128335/1/J%20Virol%2076.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/128335/1/J%20Virol%2076.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Hofmann-Lehmann Regina joint author ZORA 700 1- Vlasak Josef joint author ZORA 700 1- Chenine Agnès-Laurence joint author ZORA 700 1- Li Pei-Lin joint author ZORA 700 1- Baba Timothy W. joint author ZORA 700 1- Montefiori David C. joint author ZORA 700 1- McClure Harold M. joint author ZORA 700 1- Anderson Daniel C. joint author ZORA 700 1- Ruprecht Ruth M. joint author ZORA 773 0- Journal of Virology 76(10):5278-5284 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess