APOBEC3G and other proteins in the same family are able to act as Activation-Induced (Cytidine) Deaminases (AID). These proteins are able to induce numerous deoxycytidine to deoxyuridine mutations in the first strand negative strand of the HIV DNA primarily expressed as complementary DNA (cDNA). The hypermutation ultimately destroys the coding and replicative capacity of the virus, resulting in many inviable virions. Lentiviruses such as HIV have evolved the Viral infectivity factor (Vif) protein in order to counteract this effect. Vif interacts with APOBEC3G and triggers the ubiquitination and degradation of APOBEC3G via the proteasomal pathway.[3] APOBEC3G has a much weaker antiviral effect when its active site has been mutated to the point that the protein can no longer mutate retroviral DNA.[4]
It was first identified in 2002 as a cellular factor able to restrict replication of HIV-1 lacking the viral accessory protein Vif. Soon after, it was shown that APOBEC3G belonged to a family of proteins grouped together due to their homology with the cytidine deaminase APOBEC1.
References
- ^ Sheehy AM, Gaddis NC, Choi JD, Malim MH (August 2002). "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein". Nature 418 (6898): 646–50. doi:10.1038/nature00939. PMID 12167863.
- ^ Takaori A (December 2005). "[Antiviral defense by APOBEC3 family proteins]" (in Japanese). Uirusu 55 (2): 267–72. doi:10.2222/jsv.55.267. PMID 16557012.
- ^ Donahue JP, Vetter ML, Mukhtar NA, D'Aquila RT (July 2008). "The HIV-1 Vif PPLP motif is necessary for human APOBEC3G binding and degradation". Virology 377 (1): 49–53. doi:10.1016/j.virol.2008.04.017. PMID 18499212.
- ^ Goila-Gaur R, Strebel K (2008). "HIV-1 Vif, APOBEC, and intrinsic immunity". Retrovirology 5: 51. doi:10.1186/1742-4690-5-51. PMID 18577210.
[edit] Further reading
- Prochnow C, Bransteitter R, Klein MG, Goodman MF, Chen XS (January 2007). "The APOBEC-2 crystal structure and functional implications for the deaminase AID". Nature 445 (7126): 447–51. doi:10.1038/nature05492. PMID 17187054.
This article on a gene on chromosome 22 is a stub. |
Inga kommentarer:
Skicka en kommentar