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Immunity against endogenous retrotroviruses by APOBEC

natasa778

Senior Member
Messages
1,774
Interesting!

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576619/

… a role for APOBECs as a cellular defense system against retroviruses and retroelements. In support of this notion, the expansion of the single APOBEC3 gene in mice to the seven APOBEC3 genes found in primates apparently correlates with the significant enhancement of the restriction of endogenous retroelements seen in primates, including humans. This review discusses the current understanding of the mechanism of action of APOBEC cytidine deaminases and attempts to summarize their roles in controlling retrotransposons.


The relationship between HERV elements and human diseases has been widely discussed following the detection of various HERV genome-derived mRNA, proteins, and even viral particles in patients with several diseases (Nelson et al., 1999; Mayer, 2001; Christensen, 2010). It has also been demonstrated that HERVs exhibit complex interactions with exogenous infectious viruses, such as HIV-1 and herpesviruses (Christensen, 2010). Of note, the most recently active HERVs, known as the HERV-K family with homology to MMTV (Mayer and Meese, 2005), which were reconstituted on the basis of ancient HERV-K sequences, could be restricted by APOBEC3 proteins in an ex vivo assay for their mobility


…. Based on these findings, it is reasonable to consider that the rapid evolution of APOBEC3s in primates can be attributed to the strong positive selective pressure from their targets, endogenous retrotransposons


…. The spectrum of biological functions of the APOBEC family is expanding. Several members of this family play important roles in intrinsic immunity by regulating the spread of foreign and endogenous nucleic acids through non-editing and editing mechanisms. In doing so, they balance the beneficial and deleterious effects of retrotransposition on the host genome. While the restriction activity of the APOBEC family against retroviruses and retroelements is a fairly recent discovery, earlier studies of the zinc-dependent deaminase superfamily of both prokaryotes and eukaryotes that act on nucleosides and nucleotides have provided evidence of a complex evolutionary history. These research findings on the ancient origins of the APOBEC family, and its presence in widely divergent vertebrate lineages provide further insights into the co-evolution of the APOBEC family and retrotransposons.