Dr. Sara Sawyer will use a $120,000 grant from the Foundation for AIDS Research (amFAR) to study how the HIV virus and the cells it attacks have evolved together over time. The goal of her research is to discover new targets for drugs.
When HIV infiltrates cells, the virus hijacks its host’s genetic machinery to produce proteins and ultimately replicate itself. It has been recently found that the retrovirus hijacks about 1,000 human genes.
“The big challenge now is to find which of these 1,000 genes and the proteins they encode are critical for HIV infection,” says Sawyer, an assistant professor of molecular genetics and microbiology at The University of Texas at Austin. “Those will be good targets for blocking the virus with new antiviral drugs.”
Viruses and their hosts are constantly evolving to thwart each other in an arms race that occurs over many generations and results in evolutionary change in both.
To find the genes and proteins essential for HIV to do its work in human cells, Sawyer will look in the genomes of primates for an evolutionary record of these lockstep changes.
African primates such as chimpanzees and gorillas have been evolving with the precursor to HIV, called SIV, for millions of years. They rarely get sick from the virus. Evolutionary theory predicts that the primate genes and proteins most critical to SIV infection will have evolved more rapidly over time than other genes, as the primates evolved to sidestep the viral attack.
Sawyer will look for these proteins that have changed the fastest over time. It’s these proteins that will likely be the most important in blocking the retrovirus, and could point to new targets for HIV drug development.
“Mutations in host cell proteins that decrease the ability of retroviruses like HIV to multiply will be favored over time,” says Sawyer. “If we can identify which of these proteins have played the most important role in host resistance, then we may find new ways to block the virus and develop antivirals.”
Sawyer and her colleagues pioneered this particular method of mining evolutionary history to uncover the workings of HIV-host interactions. She also recently received a Sloan Fellowship to pursue her research.
Source: University of Texas at Austin, USA