Identification and characterization of human immunodeficiency virus 1 nef interacting novel cellular factors

Abstract

Human immunodeficiency virus (HIV) is the etiologic agent of Acquired immunodeficiency syndrome (AIDS) and has been the subject of intense investigation for last 23 years. On the basis of variation in envelope genetic sequences, HIV-1 has been classified into three major groups namely M, N, and O among which M group is responsible for the global epidemic. M group has been further divided into subtypes. Subtype B of HIV-1 predominates in North America and Europe where as subtype C predominates in Africa and South East Asia including India. According to May 2006 UNAIDS estimates, India already has the largest number of HIV-infected individuals in the world. HIV-1 codes three structural proteins Gag, Pol, and Env and two regulatory proteins Tat and Rev. In addition to these structural and regulatory proteins, viral genome also encodes accessory proteins Nef, Vif, Vpr and Vpu. Nef is a 27 kDa myristoylated protein. Following its identification, the nef gene was the center of unprecedented controversy regarding its function in the viral life cycle. Based on preliminary observations that a nef deleted virus replicated slightly better in T-cell lines as compared to the complete virus and also modestly repressed HIV transcription, nef was proposed to ``negatively´´ regulate the viral replication. Later on it was reported that nef-deleted viruses fail to replicate efficiently and do not develop symptoms of AIDS. Nef contributes in viral pathogenesis by down regulation of CD4 and MHC class I molecule preventing viral superinfection and by helping virus to evade host immune system. Nef has been also implicated in activation of T cells and making the cells permissive to virus. Even though these functions have been well studied there is controversy in literature regarding its role in viral replication and infection. Nef seems to perform most of its function by interacting with host cell factors.