In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6

Kenta Matsuda, Katsuhisa Inaba, Yoshinori Fukazawa, Megumi Matsuyama, Kentaro Ibuki, Mariko Horiike, Naoki Saito, Masanori Hayami, Tatsuhiko Igarashi, Tomoyuki Miura

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Although X4 tropic SHIVs have been studied extensively, they show distinct infection phenotypes from those of R5 tropic viruses, which play an important role in HIV-1 transmission and pathogenesis. To augment the variety of R5 tropic SHIVs, we generated a new R5 tropic SHIV from the highly pathogenic X4 tropic SHIV-KS661, a derivative of SHIV-89.6. Based on consensus amino acid alignment analyses of subtype B R5 tropic HIV-1, five amino acid substitutions in the third variable region successfully changed the secondary receptor preference from X4 to R5. Improvements in viral replication were observed in infected rhesus macaques after two passages, and reisolated virus was designated SHIV-MK38. SHIV-MK38 maintained R5 tropism through in vivo passages and showed robust replication in infected monkeys. Our study clearly demonstrates that a minimal number of amino acid substitutions in the V3 region can alter secondary receptor preference and increase the variety of R5 tropic SHIVs.

Original languageEnglish (US)
Pages (from-to)134-143
Number of pages10
JournalVirology
Volume399
Issue number1
DOIs
StatePublished - Mar 30 2010

Keywords

  • AIDS
  • CCR5 tropic
  • Mutagenesis
  • SHIV
  • V3 region

ASJC Scopus subject areas

  • Virology

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    Matsuda, K., Inaba, K., Fukazawa, Y., Matsuyama, M., Ibuki, K., Horiike, M., Saito, N., Hayami, M., Igarashi, T., & Miura, T. (2010). In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6. Virology, 399(1), 134-143. https://doi.org/10.1016/j.virol.2010.01.008