By now we (both H&V students and scientists in general) know quite a bit about HIV replication. We have studied specific proteins encoded within the retrovirus pol gene; we know how reverse transcriptase functions to incorporate viral RNA into the host cell's DNA genome; we know how retrovirus surface glycoproteins encoded in the env gene interact with immune cells. One facet of replication that we have not detailed this year, however, is the retrovirus packaging technique encoded by the gag gene.
An article recently published in Cell reveals how the Gag protein assembles copies of the retrovirus genome and viral proteins into new virus particles. The team of researchers used crosslinking-immunoprecipitation (CLIP) sequencing to observe how Gag recruits viral RNA. After Gag binds to a sequence of viral RNA known as psi, it will move to the cell's plasma membrane, undergo behavioral changes, and bind to different sites throughout the genome. Gag protein in the cytoplasm tends to bind to RNA sequences rich in guanine; at the plasma membrane, Gag is drawn to RNA sequences rich in adenine. This switch in RNA binding behavior seems to be induced by the crowding of Gag protein at the plasma membrane.
Another major discovery in the study was that Gag protein also binds to cellular tRNA, which may help regulate and pace the viral assembly process by acting as a shield against unnecessary RNA or membrane binding.