HIV-1 Nef AND HOST CELL PROTEIN KINASES

Kalle Saksela

Institute of Medical Technology, University of Tampere, P.O. Box 607, FIN-33101, Tampere, Finland

Received 11/10/97 Accepted 11/17/97

1. ABSTRACT

Nef is a 27 - 34 kD myristoylated protein unique to primate lentiviruses. A functional Nef gene is important for development of high viremia and simian AIDS in SIV infected rhesus macaques (1). Notably, animals infected with Nef-deleted attenuated viruses are resistant to subsequent challenge with pathogenic wild-type viruses (2) A critical role for Nef in development of AIDS in humans has been suggested by the observation that some individuals with a long-term nonprogressive HIV-1 infection (persons who show no clinical or immunological signs of immunodeficiency despite being HIV seropositive for over a decade) are infected with viruses carrying naturally occurring Nef deletions (3, 4). The mechanism of Nef action remains incompletely understood, but multiple lines of evidence point out to a role in modulation of cellular signaling pathways via physical and functional interactions with host cell protein kinases. These findings will be discussed in the following, preceded by a short introduction into the role of Nef in cell biology of HIV infection, which is intended to serve as a critical review of our current understanding on this enigmatic issue rather than a comprehensive review of the literature.