Retroviruses complete their life cycle by exploiting host cellular mechanisms and bypassing host restriction factors. Because of the unique life cycle based on reverse transcriptase (RT)-mediated integration/replication, retroviruses present a unique set of challenges to the host immune system; however, these viruses also routinely copy host mRNAs into new gene copies called ‘retrocopies’.
Thousands of young and old retrocopies are present in each human genome and the presence and sequence of many copies differs amongst individuals. However, retrocopies have largely been ignored as pseudogenes. The McLaughlin Lab has recently shown that human and other primate genomes contain retrocopies of the APOBEC3 family of viral restriction factors that are transcribed and capable of restricting virus replication in vitro.
More recent data from this PNRI lab suggests that retrocopies of multiple families of restriction factor genes exist in humans and other primates; they propose that within these retrocopies exist functional antiviral restriction factors that may represent the manifestation of a powerful mechanism of genome evolution to keep up with rapidly evolving viruses. Further, some of these retrocopies are likely very young–present in only some humans–and could represent an unappreciated source of individual variation in susceptibility or resistance to viral infection.
The work of the McLaughlin Lab aims to improve understanding of the long-term co-existence and the occasional co-option between retroviruses and their hosts, as well as the consequences of such processes on human disease resistance and susceptibility.