We have biochemically confirmed that APOBEC3G is a cytidine deaminase and found that the APOBEC3G induces G to A hypermutation in the newly-synthesized HIV-1. As APOBEC3G only converts cytidine (C) to unridine (U), it should edit the minus-strand viral DNA. The lethal hypermutation and the viral DNA degradation induced by APOBEC3G editing could be the major mechanism that causes APOBEC3G to inhibit HIV-1 replication. We have also found that APOBEC3G is able to induce non-lethal hypermutation in the replicating HIV-1 genome. Therefore, this host defense factor could be used by HIV-1 and contribute to the genetic variation in HIV-1 populations.

I began to study the function of HIV-1 Vif protein when I became an assistant professor of Medicine at Jefferson Medical College in 1997. Vif is a very difficult protein to handle. Gradually we have found that Vif could protect the nucleic acid of HIV-1 from the endogenous inhibitor(s). When APOBEC3G was identified as the endogenous inhibitor of HIV-1 replication that requires Vif protein to counteract, we started to examine the sequence of viral RNA and viral DNA, and found that APOBEC3G edits viral DNA.

The replication of mammalian viruses depends on a favorable balance between the beneficial and harmful effect of many host factors. A host factor APOBEC3G is a cytidine deaminase that damages the newly-synthesized HIV-1 DNA. This newly-identified mechanism is one of the methods that the human body uses to fight against various viral infections. Unfortunately, HIV-1 encodes a Vif protein to block this strong antiviral effect. Further works based upon our discovery could lead to the development of novel anti-HIV inhibitors and therefore benefit individuals infected with HIV-1.