Evasion of cytotoxic T lymphocytes is a functional constraint maintaining HIV-1 Nef expression

✍ Scribed by Ayub Ali; Hwee L. Ng; Mirabelle D. Dagarag; Otto O. Yang

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 237 KB
• Volume: 35
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200535053

✦ Synopsis

Nef expression is not required for HIV-1 replication and is highly targeted by CD8 + CTL, raising the question of why Nef expression is not lost in order to evade immunity in vivo. We explore whether MHC class I (MHC-I) down-regulation to evade CTL in general is a selective pressure maintaining Nef. HIV-1 with functional Nef (wild type, WT) is compared to virus containing a Nef point mutation (M20A) that selectively ablates MHC-I down-regulation. WT-infected cells are relatively resistant to cytolysis and less suppressed for viral replication by Gag-and RT-specific CTL compared to M20A. These viruses grow similarly in vitro in the absence of CTL, but the presence of Gag-or RTspecific CTL strongly favors WT overgrowth of M20A. Finally, while in vitro selection by Nef-specific CTL readily drives disruption of the nef reading frame, the addition of Gagor RT-specific CTL markedly limits such escape. These data indicate that MHC-I downregulation is an important function favoring Nef maintenance due to a net selective advantage in the setting of the general CTL response.