Designing a Better Model for HIV Infection
By Jeffrey Laurence, M.D.
Dr. Amit SharmaMonkey models are critical to exploring almost everything related to human HIV-1 infection, from vaccines to treatment and cure. But HIV-1 does not persistently infect the small monkeys known as macaques available for studies. Instead, these primates are susceptible to SIV—an HIV-like virus that can cause AIDS in monkeys.
Researchers study macaques infected with SHIVs—a combination of SIV and HIV—which resemble the activity of HIV in a monkey. But SHIVs have a limitation: They don’t grow well in monkey cells, partly because the viral envelope triggers production of interferons—proteins produced by the body shortly after infection that serve as a main defense against many viruses.
The Research Question
In this study, the challenge was to identify the factors involved in interferon-based limits to growth of SHIVs.
Researchers used a technique known as RNA-Seq to capture all the genes activated by interferon in macaque immune cells. By examining the proteins produced by those genes they could home in on those most likely to interfere with the HIV envelope—the viral culprit known to result in interferon production.
They identified several interferon-induced transmembrane (IFITM) proteins, which are present in macaques but not in humans. Scientists used CRISPR-Cas9 technology (a gene-editing tool) to delete IFITMs in monkey cells and saw that SHIV could grow, even in the presence of interferon. These findings confirmed that it was the IFITMs—activated by interferon—that prevented SHIVs from growing well in monkey cells.
The authors note that the study “may shed light on new approaches to improve the SHIV/macaque models by rationally designing SHIVs while maintaining as much as possible of the HIV-1 character of the virus.” It may also help to define how other viruses adapt to host restriction factors, enabling transmission across species.
Dr. Amit Sharma is an Assistant Professor at Ohio State University and is funded by amfAR.
Dr. Laurence is amfAR’s senior scientific consultant.