HIV-1 Nef and host cell protein kinases.
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. Notably, animals infected with Nef-deleted attenuated viruses are resistant to subsequent challenge with pathogenic wild-type viruses. 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. 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.
Saksela
K
K
Institute of Medical Technology, University of Tampere, P.O. Box 607, FIN-33101, Tampere, Finland. kalle.saksela @uta.fi
D000595:Amino Acid Sequence; D000818:Animals; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000201:enzymology / Q000821:virology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D054311:nef Gene Products, Human Immunodeficiency Virus; D018909:src Homology Domains / Q000235:genetics
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus; D011494:Protein Kinases