Talks on Apobec and on Lentiviral Evolution

At today's session on lentiviral diversity, Reuben Harris of the University of Minnesota gave an update on his studies of Apobec. In 2002, human Apobec3G was described as a host cell factor that inhibits HIV replication by introducing hypermutations, and HIV has evolved the Vif protein to inhibit Apobec3G by triggering its degradation. Apobec3G can therefore restrict replication of cells with HIV lacking Vif. By now, several additional Apobec3s have been described, but it has been unclear as to which ones contribute to HIV restriction. Harris presented evidence that four Apobec3s, Apobec3D, F, G and H all contribute to HIV restriction. “There is controversy surrounding every single Apobec except for Apobec3G,” Harris said. “So this work should, I hope, resolve that controversy. [We show that] those four are involved, the rest are not involved.”  

The fact that four Apobec3s are involved in causing hypermutation in HIV could mean that drugs that inhibit Vif might unleash even more Apobec-driven hypermutation in HIV than previously thought, Harris said. “The idea is if you can figure out a way to stop Vif from functioning, then you can unleash this swarm of Apobecs, and that will kill the virus,” he said. On the other hand, inhibiting Apobec might lead to fewer mutations as HIV replicates, which might result in a reduced ability of HIV to escape the immune response.

Viral evolution was discussed at the session as well, and Aris Katzourakis of the University of Oxford showed that lentiviruses, the genus HIV belongs to, might be much older than previously thought. Katzourakis and his colleagues looked at an endogenous lentivirus called RELIK, which has integrated into the rabbit genome, and searched for a similar integrated endognous lentivirus in hares. They found Relik in exactly the same genomic location in both the rabbit and the hare. “We know that the [evolutionary] split between the rabbits and the hare happened 12 million years ago,” Katzourakis said. “So for a virus to be in exactly the same location in these two really different animals [means that they] must have gotten in there before the two species diverged.” This means that lentiviruses must be at least 12 million years old, much older than previous estimates which ranged between thousands of years up to a million years. This suggests that what we see today in terms of the interactions between the virus and their host has been shaped by conflict between viruses and their host that go back a long time, Katzourakis said.