Yerkes research core is key to HIV study in Nature

Woodruff Health Sciences Center | July 22, 2014

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Lisa Newbern
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In a study reported in Nature this month, Yerkes National Primate Research Center researchers were key in determining that treating SIV-infected rhesus macaques with type 1 interferon, a protein known to trigger antiviral responses and inflammation, can have beneficial and detrimental effects on the development of disease.

The Yerkes researchers used high-tech RNA-sequencing technology to study genome-wide expression (transcriptome) of antiviral responses in monkey tissues during various stages of the study. This work was critical to determining that blocking interferon at the onset of infection may be a viable strategy for treating HIV-related disease, but equally important is giving consideration to the viral status of each patient because interferon blockade may trigger a rebound in virus levels in chronic infection.

Steve Bosinger, PhD, a Yerkes researcher, co-director of the Yerkes Nonhuman Primate Genomics Core and a study co-author, 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."

To do this, the researchers used a new version of the rhesus macaque genome that has three times the number of annotated genes than what has been available.

Interferon is the central, crucial component of an innate immune response against viruses. Most viral infections are cleared or are controlled in a few weeks and the interferon response stops. In HIV/SIV, however, the infection persists indefinitely, and the interferon response goes on as well. Because of this, scientists have speculated for years that interferon itself may be a significant contributor to disease in people infected with HIV. In the Nature study, the researchers tested this directly by giving interferon to one group of monkeys and administering an inhibitor in a second group of animals.

The study's lead authors are Daniel Douek, MD, PhD, Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Disease, and Netanya Sandler, MD, Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch at Galveston. Robert Norgren, PhD, Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, provided the rhesus genome reference. Greg Tharp, Msc, a bioinformaticist in the Yerkes Nonhuman Primate Genomics Core, also contributed to the study. Bosinger says the Yerkes Core will perform the genomics components of Douek's follow-up studies, which will examine the effect of interferon blockade on chronic infection and in animals receiving anti-retroviral therapy.

Established in 1930, the Yerkes National Primate Research Center paved the way for what has become the National Institutes of Health-funded National Primate Research Center (NPRC) program. For more than eight decades, the Yerkes Research Center has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve human health and well-being. Today, the Yerkes Research Center is one of only eight NPRCs. The center provides leadership, training and resources to foster scientific creativity, collaboration and discoveries, and research at the center is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.

Within the fields of microbiology and immunology, neurologic diseases, neuropharmacology, behavioral, cognitive and developmental neuroscience, and psychiatric disorders, the center's research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases; understand the basic neurobiology and genetics of social behavior and develop new treatment strategies for improving social functioning in social disorders such as autism; interpret brain activity through imaging; increase understanding of progressive illnesses such as Alzheimer's and Parkinson's diseases; unlock the secrets of memory; treat drug addiction; determine how the interaction between genetics and society shape who we are; and advance knowledge about the evolutionary links between biology and behavior.