CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef

Takamasa Ueno, Chihiro Motozono, Sachi Dohki, Philip Mwimanzi, Susanne Rauch, Oliver T. Fackler, Shinichi Oka, Masafumi Takiguchi

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)


HIV-1 Nef plays multiple roles in modulating immune responses, even though it is a dominant CTL target itself. How Nef accomplishes the balance between such conflicting selective pressures remains elusive. By genetic and functional studies, we found that Arg75Thr and Tyr85Phe mutations, located in a well-conserved proline-rich region in Nef, were differently associated with escape from CTL responses specific for two overlapping HLA-B35-restricted epitopes. CTLs specific for an epitope, that selected Tyr85Phe, were elicited earlier and had more potent functional avidities than did those that selected Arg75Thr. Although the double mutant could escape from both CTLs, the mutations are rarely observed in combination naturally. Introduction of both mutations reduced Nef's HLA class I down-regulation activity and increased the susceptibility of virus-infected cells to recognition by CTLs targeting other epitopes. Moreover, the mutant Nef was impaired in the association with activated cellular kinases and in the enhancement of viral replication. These results highlight CTL immunosurveillance as important modulators of Nef's biological activity in the infected host.

Original languageEnglish
Pages (from-to)1107-1116
Number of pages10
JournalJournal of Immunology
Issue number2
Publication statusPublished - Jan 15 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 Nef'. Together they form a unique fingerprint.

Cite this