Nef (protein)
Encyclopedia
Nef is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 expressed by primate lentiviruses. These include human immunodeficiency viruses (HIV-1 and HIV-2) and simian immunodeficiency virus
Simian immunodeficiency virus
Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

 (SIV). Nef is one of many pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

-expressed proteins, known as virulence factor
Virulence factor
Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...

s, 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
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

 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
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...

-I (MHC I) and MHC II present on antigen presenting cells (APCs) and target cells, CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...

 and CD28
CD28
CD28 is one of the molecules expressed on T cells that provide co-stimulatory signals, which are required for T cell activation. CD28 is the receptor for CD80 and CD86 . When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen presenting cells...

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.
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