Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation

The N-terminal alpha-helix domain of the human immunodeficiency virus type 1 (HIV-1) Nef protein plays important roles in enhancement of viral infecti vity, virion incorporation of Nef, and the down-regulation of major histoco mpatibility complex class I (MHC-I) expression on cell surfaces. In this st udy, we demonstrated that Met 20 in the alpha-helix domain was indispensabl e for the ability of Nef to modulate MHC-I expression but not for other eve nts. We also showed that Met 20 was unnecessary for the down-regulation of CD4. These findings indicate that the region governing MHC-I down-regulatio n is proximate in the alpha-helix domain but is dissociated functionally fr om that determining enhancement of viral infectivity, virion incorporation of Nef, and CD4 down-regulation.