The ability to regulate and even target mutagenesis is an extremely valuable cellular asset. Enzyme-catalyzed DNA cytosine deamination is a molecular strategy employed by vertebrates to promote antibody diversity and defend against foreign nucleic acids. Ten years ago, a family of cellular enzymes was first described with several proving capable of deaminating DNA and inhibiting HIV-1 replication. Ensuing studies on the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) restriction factors have uncovered a broad-spectrum innate defense network that suppresses the replication of numerous endogenous and exogenous DNA-based parasites. Although many viruses possess equally elaborate counter-defense mechanisms, the APOBEC3 enzymes offer a tantalizing possibility of leveraging innate immunity to fend off viral infection. Here, we focus on mechanisms of retroelement restriction by the APOBEC3 family of restriction enzymes, and we consider the therapeutic benefits, as well as the possible pathological consequences, of arming cells with active DNA deaminases.
|Title of host publication
|Number of pages
|Published - 2013
|Current Topics in Microbiology and Immunology
Bibliographical noteFunding Information:
We thank J. Hultquist and A. Land for comments, and B. Leonard for Fig.3b. We apologize to colleagues whose work could not be cited due to space limitations. Support was provided by grants from the National Institutes of Health R01-AI064046 and P01-GM091743 to RSH and F31-DA033186 to EWR.