Nef (protein)

Source: Wikipedia, the free encyclopedia.
Not to be confused with Nucleotide exchange factor or S100B.
Negative factor, (F-Protein) or Nef
SCOP2
1avv / SCOPe / SUPFAM
OPM superfamily269
OPM protein2nef
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Nef (Negative Regulatory Factor) is a small 27-35 kDa myristoylated

virulence factors, which function to manipulate the host's cellular machinery and thus allow infection, survival or replication of the pathogen.[1] Nef stands for "Negative Factor" and although it is often considered indispensable for HIV-1 replication, in infected hosts the viral protein markedly elevates viral titers.[2]

Function

The expression of Nef early in the viral life cycle ensures

CD4+ lymphocytes, but is not sufficient to cause activation in the absence of exogenous stimuli.[3]

By down regulating cell surface expression of

Interleukin-2 (IL-2).[5]
Since IL-2 is known to activate the growth, proliferation, and differentiation of T-cells to become effector T-cells; this is a self-serving effect that creates a new population of cells which HIV-1 is able to infect. Self-activation of the infected cell by IL-2 also stimulates the cell to become an effector cell and initiate the machinery which HIV-1 relies upon for its own proliferation.

To further evade the host immune response, Nef down-regulates the cell surface and total expression of the negative immune modulator

proapoptotic member of the Bcl-2 family thus protecting the infected cells from apoptosis.[citation needed
]

Cytoskeletal remodeling is thought to reduce TCR signaling during early infection and is also modulated to some degree by Nef.

cofilin
and interferes with early TCR signaling.

Clinical significance

The Sydney blood bank cohort (SBBC) were a group of eight patients who were asymptomatic many years after initial infection by transfusion from an infected blood donor. Later analyses showed that the virus strain was a Nef-deleted variant.[7]

Vaccine

A Nef-deleted virus vaccine has not been tried in humans although it was successfully tested in Rhesus macaques.[8][9]

See also

  • HIV structure and genome

References

  1. PMID 15817946. Archived from the original
    (PDF) on 2017-08-10. Retrieved 2008-08-07.
  2. ^ Marcey D, Somple M, Silva N (2007-01-01). "HIV-1 Nef Protein". The Online Macromolecular Museum Exhibits. California Lutheran University. Retrieved 2008-08-06.
  3. PMID 23227982
    .
  4. PMID 20594957
    .
  5. PMID 11463741
    .
  6. PMID 23372701
    .
  7. PMID 10352163
    .
  8. PMID 1470917
    .
  9. PMID 15928037
    .

Further reading

External links
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