%0 Journal Article
%T Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142
%A Kevin C Olivieri
%A Robert M Scoggins
%A Brooks Broderick
%A Maria LC Powell
%A Melissa A Alexander
%A Marie-Louise Hammarskj£żld
%A David Rekosh
%A David Camerini
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-42
%X The nef gene of HIV-1 plays a pivotal role in the pathogenesis of AIDS [4-8]. For example, patients infected with nef-deleted HIV-1 exhibited much slower progression to AIDS [6,9-11]. The nef gene is important for viral replication in mature T cells [12-16] and macrophages [14,17-19]. When thymocytes are infected, Nef plays a role in increasing the cytopathic nature of the virus [20-24]. The importance of Nef is further corroborated by observations of immune dysfunction in nef-transgenic mice [25-28].Several functions have been assigned to Nef although the role of each in disease progression has not been firmly established (for reviews see: [21,29-37]). We chose to focus on Nef's abilities to downmodulate CD4 [38] and cell surface MHC-I A and B molecules [39,40], and its ability to enhance viral infectivity [12,41,42]. These functions have been well studied by several labs and in various cell types and systems [17,43-50]. Nef mediated enhancement of infectivity may be due to Nef downmodulation of cell surface CD4, allowing more efficient Env incorporation into HIV-1 particles [51,52]. Enhancement of infectivity may also occur when Nef is present in CD4 negative producer cells [12,53-56]. In this case, enhancement appears to act at a post-entry, pre-integration step in the viral life cycle [57,58] and may be related to interaction of the viral pre-integration complex with the actin cytoskeleton [59]. Downmodulation of MHC-I A and B molecules protects cells from lysis by HIV-1 specific cytotoxic T cells [40]. The ability to avoid the immune system may be important in establishment and maintenance of infection.Kirchhoff and colleagues compared the predicted amino acid sequences of Nef proteins from progressors with those of non-progressors and found that certain residues characterize Nef sequences from each type of patient [1]. When compared to non-progressor Nefs, progressor Nefs were better able to downmodulate CD4 and less able to downmodulate MHC-I molecules, and a
%U http://www.retrovirology.com/content/5/1/42