Nef protein (HIV-1) (Nef)

The Nef protein (HIV-1), or Negative Regulatory Factor, is a small 27-35 kDa myristoylated viral accessory protein encoded by HIV-1 and other primate lentiviruses, localizing primarily to the cytoplasm and plasma membrane. It plays a critical role in viral pathogenesis by downregulating cell surface expression of CD4 and MHC class I molecules, thereby evading host immune detection and promoting virus release. Nef also counters host restriction factors like SERINC5 and SERINC3, enhancing virion infectivity by preventing fusion pore enlargement that inhibits viral entry. Additional functions include lowering the activation threshold of CD4+ T cells, retargeting kinases like Lck to endosomes, and inactivating proapoptotic proteins such as Bad to protect infected cells. Early studies debated its role as a transcriptional repressor of the HIV-1 LTR, but this has been largely refuted, with its primary effects on host cell modulation confirmed. Overall, Nef is indispensable for high viral loads in vivo despite not being an enzymatic therapeutic target.

Other names

Negative Regulatory FactorNegative FactorF protein3'-orfB-ORF