Nef Protein in Hiv
The role of the accessory NEF protein in HIV infection
Kanokporn Tangthamvanich Department of Microbiology and Immunology University of Otago [Word count: 895]
The role of the accessory NEF protein in HIV infection
In human immunodeficiency virus (HIV) infection, there is one essential virulence protein, the Nef protein, which is identified as a negative factor due to it having a negative effect on viral replication (1). It performs critical functions in the host during the viral life cycle. The Nef protein is only active during the early stages of the HIV infection (2). It primarily enhances viral replication, infectivity and pathogenesis. Therefore, Nef has a crucial role in HIV infection as it is based mainly on the Nef performance to downregulate CD4, from the cell surface, and major histocompatibility complex class I (MHC-I), the important surface molecules in T-cell activation (3). In one study they demonstrate that if the cells susceptible to HIV infection, the products of accessory gene can change severity of viral infection (4). Rhesus monkey were tested and demonstrated that a Nef gene is crucial for reaching high virus loads and development of AIDS-like disease in animals (5). Nef is a 206 amino acid myristoylated peripheral membrane protein (6). It consists of a core domain, an anchor domain and two flexible loops which are located at the N terminus and near the C terminus (7). Nef-core domain has a type II polyproline for Scr family kinase to bind. Various host cell signaling pathways are influenced by Nef to promote HIV-1 replication in AIDS pathogenesis (4). To enhance infectivity through signaling pathway, Nef needs to directly interact with the Scr family of protein tyrosine kinases such as Hck and Lyn, Lck and Fyn (8). There is a PxxP binding motif of Src homology region 3 (SH3) domain which is present in Nef, that plays an important role in promoting viral replication (8). The best understood phenotypic effect of Nef is the downregulation
Kanokporn Tangthamvanich Department of Microbiology and Immunology University of Otago [Word count: 895]
The role of the accessory NEF protein in HIV infection
In human immunodeficiency virus (HIV) infection, there is one essential virulence protein, the Nef protein, which is identified as a negative factor due to it having a negative effect on viral replication (1). It performs critical functions in the host during the viral life cycle. The Nef protein is only active during the early stages of the HIV infection (2). It primarily enhances viral replication, infectivity and pathogenesis. Therefore, Nef has a crucial role in HIV infection as it is based mainly on the Nef performance to downregulate CD4, from the cell surface, and major histocompatibility complex class I (MHC-I), the important surface molecules in T-cell activation (3). In one study they demonstrate that if the cells susceptible to HIV infection, the products of accessory gene can change severity of viral infection (4). Rhesus monkey were tested and demonstrated that a Nef gene is crucial for reaching high virus loads and development of AIDS-like disease in animals (5). Nef is a 206 amino acid myristoylated peripheral membrane protein (6). It consists of a core domain, an anchor domain and two flexible loops which are located at the N terminus and near the C terminus (7). Nef-core domain has a type II polyproline for Scr family kinase to bind. Various host cell signaling pathways are influenced by Nef to promote HIV-1 replication in AIDS pathogenesis (4). To enhance infectivity through signaling pathway, Nef needs to directly interact with the Scr family of protein tyrosine kinases such as Hck and Lyn, Lck and Fyn (8). There is a PxxP binding motif of Src homology region 3 (SH3) domain which is present in Nef, that plays an important role in promoting viral replication (8). The best understood phenotypic effect of Nef is the downregulation