A novel motif in HIV-1 Nef that regulates MIP-1beta chemokine release in macrophages.
All primate lentiviruses encode Nef, an accessory protein that is important for viral pathogenicity in vivo. Lentiviral Nef proteins regulate the release of chemokines (MIP-1 alpha/beta) from infected macrophages, thereby enhancing virus dissemination (S. Swingler, A. Mann, J. Jacque, B. Brichacek, V. G. Sasseville, K. Williams, A. A. Lackner, E. N. Janoff, R. Wang, D. Fisher, and M. Stevenson, Nat. Med. 5:997-1003, 1999). In the current study, we have identified a novel domain within Nef (K(92)EK) that is required for Nef-dependent MIP-1beta production by infected macrophages. Mutations in this domain abrogated MIP-1beta induction but did not affect other Nef-ascribed activities, such as CD4 or major histocompatibility complex (MHC) class Iota downregulation. This further underscores Nef as a modular protein with genetically separable activities that may contribute to its role in viral replication and pathogenicity.
Dai
Lue
L
University of Massachusetts Medical School, Program in Molecular Medicine, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
Stevenson
Mario
M
D000595:Amino Acid Sequence; D054407:Chemokine CCL4 / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*
D054407:Chemokine CCL4; D037521:Virulence Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1