The HIV-1 Virulence Factor Nef as a New Therapeutic Target Against HIV/AIDS

ABSTRACT

Human immunodeficiency virus-1 (HIV-1) encodes an accessory protein Nef.Initially, Nef had been known as a viral negative factor due to its no-effect on viral replication in the cancerous cell line system, however the pivotal role of Nef in disease progression has been discovered in primary culture and in vivo studies.The Nef protein is 27-35kDa, which is N-myristolated to attach on the intracellular membrane. Since it is already known that the nef-deleted virus is associated with long-term non-progression (LTNP), the roles of Nef linked to viral virulence were emphasized to develop an agent capable of inhibiting the progression of acquired immunodeficiency syndrome (AIDS). Nef plays multifaceted roles in host cell activities, which are recognized as the key functions of Nef-induced AIDS progression. Nef down-regulates the surface expression of several immune proteins including CD4, major histocompatibility complex class I (MHC-I/II), CD3. CD62L CXCR4, etc. Also, Nef disturbs the actin dynamics linked to vesicle trafficking and cell movement, and modulates the T-cell activation signaling associated with viral transcription. Here, we overview the molecular mechanisms of Nef with regard to AIDS pathogenesis and discuss various therapeutic approaches targeting Nef with a view to developing a new class of anti-AIDS agent capable of preventing the disease progression linked to Nef-induced CD4 down-regulation and HIV-1 replication.