Nef (protein)

Negative factor, (F-Protein) or Nef
NMR structure of the NEF protein based on the PDB 2NEF coordinates.
Identifiers
Symbol	F-protein
Pfam	PF00469
InterPro	IPR001558
SCOP	1avv
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

Nef (Negative Regulatory Factor) 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.^[1] Nef stands for "Negative Factor".^[2]

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.

HIV genome

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.^[3]

Vaccine

A nef-deleted virus vaccine has not been tried in humans although was successfully tested in Rhesus macaques.^[4][5]

See also

• HIV structure and genome

References

1. ^ Das SR, Jameel S (April 2005). "Biology of the HIV Nef protein". Indian J. Med. Res. 121 (4): 315–32. PMID 15817946. http://www.icmr.nic.in/ijmr/2005/April/0409.pdf. 
2. ^ Marcey D, Somple M, Silva N (2007-01-01). "HIV-1 Nef Protein". The Online Macromolecular Museum Exhibits. California Lutheran University. http://www.callutheran.edu/Academic_Programs/Departments/BioDev/omm/hiv1nef/molmast.htm. Retrieved 2008-08-06. 
3. ^ Learmont JC, Geczy AF, Mills J, Ashton LJ, Raynes-Greenow CH, Garsia RJ, Dyer WB, McIntyre L, Oelrichs RB, Rhodes DI, Deacon NJ, Sullivan JS' (June 1999). "Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort". N. Engl. J. Med. 340 (22): 1715–22. doi:10.1056/NEJM199906033402203. PMID 10352163. 
4. ^ Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC (December 1992). "Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene". Science 258 (5090): 1938–41. doi:10.1126/science.1470917. PMID 1470917. 
5. ^ Muthumani K, Choo AY, Hwang DS, Premkumar A, Dayes NS, Harris C, Green DR, Wadsworth SA, Siekierka JJ, Weiner DB (September 2005). "HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation". Blood 106 (6): 2059–68. doi:10.1182/blood-2005-03-0932. PMC 1895138. PMID 15928037. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1895138. 

Further reading

• Piguet V, Trono D (1999). "The Nef protein of primate lentiviruses". Rev. Med. Virol. 9 (2): 111–20. doi:10.1002/(SICI)1099-1654(199904/06)9:2<111::AID-RMV245>3.0.CO;2-P. PMID 10386338. 
• Janardhan A, Swigut T, Hill B et al. (January 2004). "HIV-1 Nef Binds the DOCK2–ELMO1 Complex to Activate Rac and Inhibit Lymphocyte Chemotaxis". PLoS Biol. 2 (1): e6. doi:10.1371/journal.pbio.0020006. PMC 314466. PMID 14737186. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=314466. 

External links

• Michael Smith. "HIV protein hides infected cells from immune system". MedPageToday.com. http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/11080. Retrieved 2008-09-26. 

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