In a new study published in this month’s Nature magazine, in which Netanya Sandler, MD, Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch at Galveston and Daniel Douek, MD, PhD, Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Disease served as lead authors, Yerkes National Primate Research Center scientists were able to determine that treating SIV-infected rhesus macaques with type 1 interferon, a protein that triggers antiviral responses and inflammation, can have both beneficial and detrimental effects on the development of disease.
Researchers working in this Yerkes-led study used high-tech RNA-sequencing technology in order to study genome-wide expression, known as transcriptome, of antiviral responses in monkey tissues throughout the stages of the study. This research was crucial in determining that, although blocking interferon at the onset of infection may be a viable strategy in the treatment of HIV-related diseases, it is equally important to consider the viral status of each patient, since interferon blockade may trigger a rebound in virus levels in chronic infection.
Steve Bosinger, PhD, co-director of the Yerkes Nonhuman Primate Genomics Core and one of the study co-authors, says, “Using genomic technology was critical to the study because the interferon system works by inducing hundreds of different antiviral genes. Genomics, rather than single-gene approaches, is needed to adequately assess the viability of the treatment blockade. Using genomics allowed us to identify novel pathways that were perturbed by blocking interferon signaling.”
In this study, a new version of the rhesus macaque genome was used, which has three times the number of annotated genes than previously available versions.
Interferon is the central, most important component of an innate immune response against viruses. The interferon response stops in a few weeks, when most viral infections are cleared or controlled. The HIV/SIV infection, however, persists indefinitely, so the interferon response continues as well. Due to this characteristic of interferon, scientists have wondered for years whether it could be a significant contributor to disease in people infected with HIV. This newly-published study tested this directly, since researchers were giving interferon to one group of monkeys, while a second group was being administered an inhibitor.
Along with Daniel Douek and Netanya Sandler, mentioned above, other researchers involved in the study include Robert Norgren, PhD, Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, who provided the rhesus genome reference, and Greg Tharp, Msc, a bioinformaticist in the Yerkes Nonhuman Primate Genomics Core. Bosinger informed the Yerkes Core will perform the genomics components of Douek’s follow-up studies, which will address the effect of interferon blockade on chronic infection and in animals receiving anti-retroviral therapy as well