Phosphorylation of HIV Nef by cAMP-dependent protein kinase

• Published in: Virology (New York, N.Y.) N.Y.), 2005-01, Vol.331 (2), p.367-374
• Main Authors: Li, Pei Lin, Wang, Tao, Buckley, Kathleen A., Chenine, Agnès-Laurence, Popov, Sergei, Ruprecht, Ruth M.
• Format: Article
• Language: English
• Subjects: Cell Line; Cyclic AMP-Dependent Protein Kinases - metabolism; Gene Products, nef - metabolism; HIV; HIV - metabolism; Human immunodeficiency virus; Humans; Leukocytes, Mononuclear - immunology; Nef; nef Gene Products, Human Immunodeficiency Virus; Phosphorylation; PKA; Protein kinase; Simian immunodeficiency virus; Simian Immunodeficiency Virus - physiology; SIV; Virus Replication
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2004.11.004

Nef, a multifunctional accessory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), is important for disease progression. Nef downmodulates CD4 and MHC class I expression, alters host-cell signal transduction pathways, and enhances viral replication. We have identified a novel interaction between Nef and cAMP-dependent kinase (PKA). N-terminal serine residues Ser 6,9 of HIV NL4-3 Nef and Ser 10 of SIVmac239 Nef were phosphorylated by PKA in a cell-free system; intracellularly, only Ser 9 of HIV NL4-3 Nef was phosphorylated by PKA. Mutation of Ser 9 to alanine in the context of full-length HIV NL4-3 lowered HIV replication in resting peripheral blood mononuclear cells (PBMC) compared to parental virus. As this mutation played a major role in abrogating the Nef effect on HIV replication in unstimulated primary cells, we postulate that Nef phosphorylation by PKA is an important step in the viral life cycle in resting cells.