Retroviruses integrated into the genome can teach us about HIV

Chimp endogenous retrovirus 2, or CERV 2, is an ancient virus that first infected chimpanzees after the Old World primate line diverged from that of humans several millions of years ago. Humans are not infected by the virus, and scientists are interested in knowing why, hoping that understanding the evolution of retroviruses and host resistance in chimps will unlock treatments and potential vaccine targets for retroviruses that do infect humans, like HIV.

Endogenous viruses are viruses that have integrated into the host genome (some refer to them as fossil viruses). An estimated 8 to 10 percent, if not more, of each mammalian genome consists of such retrotransposable elements. Chimp endogenous retrovirus 2, or CERV 2, is an ancient virus that first infected chimpanzees after the Old World primate line diverged from that of humans several millions of years ago. Humans are not infected by the virus, and scientists are interested in knowing why, hoping that understanding the evolution of retroviruses and host resistance will unlock treatments and potential vaccine targets for retroviruses that do infect humans, like HIV.

Retroviruses are different from other viruses in that their genetic code is RNA instead of DNA. This requires additional steps for replication after infection. Viruses are obligate parasites – they require the host’s machinery to replicate and survive, they cannot do so on their own. Retroviruses insert their genetic code into the host cells for its own survival, and the potential for integration into the host genome has been considered intuitive.

Out of 42 families of endogenous retroviruses in chimps, only two, CERV 1 and CERV 2, have not been found to have human orthologs (that is, a corresponding genomic element). CERV 2 has also been found in the genomes of gorilla and other old world monkeys, but not orangutans and new world monkeys. For the viral element to be integrated into the genome, the virus had to have once been capable of infecting that species. The lack of the viral element in some species also indicates that it could not infect those species. The difference in the virus’s ability to infect a species could be caused by the  manner in which the virus is transmitted (for example, biting, so it infects monkeys more readily than humans), the conditions for transmission (for example, some pathogens spread only in low hygiene conditions), and/or genetic elements, including cell surface receptors.

A team of retrovirologists at Rockefeller University identified a receptor that may be responsible for the infection of chimp cells by CERV2, copper transport protein 1 (CTR1). They published their findings in the Proceedings of the National Academy of Sciences in October 2010, and many have referred to the study as “reviving” an ancient virus. According to PhysOrg, the team had previously identified two proteins on human cells that protect against retrovirus infection, but they had not previously been able to determine why chimp cells were susceptible to CERV. However, the research group did find (2008, PLoSPathogens) that the protein APOBEC3 restricts retrovirus replication in some primates by applying mutational pressure, a mechanism potentially at work in humans.