HIV-1 Nef control of cell signalling molecules: Multiple strategies to promote virus replication
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HIV-1 has at its disposal numerous proteins encoded by its genome which provide the required arsenal to establish and maintain infection in its host for a considerable number of years. One of the most important and enigmatic of these proteins is Nef. The Nef protein of HIV-1 plays a fundamental role in the virus life cycle. This small protein of approximately 27 kDa is required for maximal virus replication and disease progression. The mechanisms by which it is able to act as a positive factor during virus replication is an area of intense research and although some controversy surrounds Nef much has been gauged as to how it functions. Its ability to modulate the expression of key cellular receptors important for cell activation and control signal transduction elements and events by interacting with numerous cellular kinases and signalling molecules, including members of the Src family kinases, leading to an effect on host cell function is likely to explain at least in part its role during infection and represents a finely tuned mechanism where this protein assists HIV-1 to control its host.
KeywordsHIV-1 Nef pathogenesis signal transduction
p21-activated kinase 2
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- Collins K L, Chen B K, Kalams S A, Walker B D and Baltimore D 1998 HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes;Nature (London) 391 397–401Google Scholar
- Deacon N J, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker D J, McPhee D A, Greenway A L, Ellett A, Chatfield C, Larison V A, Crowe S, Maerz A, Sonza S, Learmont J, Sullivan J S, Cunningham A, Dwyer D, Dowton D and Mills J 1995 Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients [see comments];Science 270 988–991PubMedGoogle Scholar
- Garcia J V and Miller A D 1991 Serine phosphorylation-independent downregulation of cell-surface CD4 by nef;Nature (London) 350 508–511Google Scholar
- Geleziunas R, Xu W, Takeda K, Ichijo H and Greene W C 2001 HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell;Nature (London) 410 834–838Google Scholar
- Greenway A L, McPhee D A, Grgacic E, Hewish D, Lucantoni A, Macreadie I and Azad A 1994 Nef 27, but not the Nef 25 isoform of human immunodeficiency virus-type 1 pNL4.3 down-regulates surface CD4 and IL-2R expression in peripheral blood mononuclear cells and transformed T cells;Virology 198 245–256PubMedGoogle Scholar
- Hanna Z, Weng X, Kay D G, Poudrier J, Lowell C and Jolicoeur P 2001 The pathogenicity of human immunodeficiency virus (HIV) type 1 Nef in CD4C/HIV transgenic mice is abolished by mutation of its SH3-binding domain, and disease development is delayed in the absence of Hck;J. Virol. 75 9378–9392PubMedGoogle Scholar
- Le Gall S, Erdtmann L, Benichou S, Berlioz-Torrent C, Liu L, Benarous R, Heard J M and Schwartz O 1998 Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules;Immunity 8 483–495Google Scholar
- Le Gall S, Heard J M and Schwartz O 1997 Analysis of Nefinduced MHC-I endocytosis;Res. Virol. 148 43–47Google Scholar
- Mangasarian A, Piguet V, Wang J K, Chen Y L and Trono D 1999 Nef-induced CD4 and major histocompatibility complex class I (MHC-I) down-regulation are governed by distinct determinants: N-terminal alpha helix and proline repeat of Nef selectively regulate MHC-I trafficking;J. Virol. 73 1964–1973PubMedGoogle Scholar
- Moarefi I, LaFevre-Bernt M, Sicheri F, Huse M, Lee C H, Kuriyan J and Miller W T 1997 Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement [see comments];Nature (London) 385 650–653Google Scholar