Nef (protein)

Nef ( Ne gative Regulatory F actor) is a protein expressed by primate lentiviruses. These include human immunodeficiency viruses (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV). Nef is one of many pathogen-expressed proteins, known as virulence factors, which function to manipulate the host's cellular machinery and thus allow infection, survival or replication of the pathogen. Nef stands for "Negative Factor".

Function
The expression of Nef early in the viral life cycle ensures T cell activation and the establishment of a persistent state of infection, two basic attributes of HIV infection. Nef also promotes the survival of infected cells by downmodulating the expression of several surface molecules important in host immune function. These include major histocompatibility complex-I (MHC I) and MHC II present on antigen presenting cells (APCs) and target cells, CD4 and CD28 present on CD4+ T cells.



Clinical significance
One group of patients in Sydney were infected with a nef-deleted virus and took much longer than expected to progress to AIDS.

Vaccine
A nef-deleted virus vaccine has not been tried in humans although was successfully tested in Rhesus macaques.