My view is that its citation frequency reflects the number of groups drawn to working on this area! Our initial publication described a gene which defines a new mechanism of cellular resistance to HIV infection. This mechanism is based on the editing (or mutation) of viral sequences by a human enzyme called APOBEC3G. This work is interesting from the perspectives of basic biology, HIV pathogenesis, and possible future HIV therapeutics. Hence, the level of general interest!

Human cells have evolved assorted ways to resist invasion by pathogens such as HIV. Some of these are fast-acting (or innate) whereas others have to be induced and are slower (or adaptive). This paper identified a new mechanism of innate cell-based resistance to HIV. The gene that is responsible, now called APOBEC3G, works by mutating and destroying the genetic material of HIV through a process known as cytidine deamination. HIV is normally protected from APOBEC3G by one of its own proteins, Vif. Pharmacologic disruption of Vif function could unlock the natural anti-HIV effects of APOBEC3G and, therefore, should be considered as a possible therapeutic strategy for treating or preventing HIV/AIDS.

My lab studies HIV replication using cell culture models. We had been studying a viral gene, called Vif, for about 10 years. We had proposed that Vif works by suppressing a cellular (or innate) anti-HIV mechanism or pathway. We had set out several years earlier to identify such genes, and the paper describes the successful outcome of these endeavors.