We use biochemical, biophysical, and structural techniques such as Nuclear Magnetic Resonance (NMR) and X-ray crystallography to improve our understanding of how one type of virus, the retrovirus, proliferates and thrives. HIV (human immunodeficiency virus) is an example of a retrovirus. Unlike most living things, viruses do not have cells that divide; new viruses are assembled in the infected host cell. The host cell is then forced to produce many thousands of identical copies of the original virus.
Deoxyribonucleic acid (DNA) contains the instructions needed for an organism to develop, survive, and reproduce. To carry out these functions, DNA sequences must be converted into messages that can be used to produce proteins. In most viruses, DNA is transcribed to ribonucleic acid (RNA), and then RNA is translated into protein. Retroviruses function differently. The RNA of retroviruses is reverse-transcribed into DNA, which is integrated into the host cell’s genome and then undergoes the usual transcription and translational processes to express the genes carried by the virus.
We focus especially on the role of one key protein: integrase. By what means does it process the ends of the viral DNA and insert them into host DNA? How is this process interrupted? We have identified a cellular protein, barrier-to-integration factor (BAF), that causes viral DNA to compact so that integration into the host cell is no longer possible.