University of Utah Health received a National Institutes of Health (NIH) renewal grant to continue funding for the Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH). This $24 million grant, which will be distributed over five years, will empower research efforts to explore the fundamental structural biology of the HIV virus, from replication to infection.
"Some problems are so interdisciplinary and so large that it is difficult for any single lab to tackle them effectively," said Wes Sundquist, Ph.D., co-chair of the Department of Biochemistry at U of U Health and the principal investigator leading the CHEETAH Center. "We need a deep understanding of the virus at the molecular level to benefit clinical applications."
The CHEETAH Center, while housed at U of U Health, also collaborates with scientists from eight other academic institutions to tackle the fundamental science behind the virus-host interaction.
The renewal funding will allow the researchers to expand on their understanding of:
- the steps the virus follows from entering the host cell to integrating into its DNA;
- how envelope viruses, like HIV, leave the host cell, and the innate immune factors in the cell that can block viral exit;
- how small reservoirs of the virus survive in the body, even during drug treatment; and
- tools to visualize the virus in three dimensions and visualize how the virus interacts with the immune system.
The HIV virus weakens a person's immune system by destroying T cells that fight disease and infection. While no cure exists, available treatments have largely relegated the virus to a chronic status in first world countries. The U.S. Department of Health and Human Services (HHS) estimate that by the end of 2015 more than 36 million people were living with the virus globally, but only about half had access to antiretroviral drug therapy.
Like other viruses, HIV interacts extensively with pathways within the host cell during its life cycle. The CHEETAH Center has the ability to explore and visualize these critical host-virus interactions, which helps to identify attractive targets for therapeutic intervention, not only for HIV, but also in other areas of human health.
According to Sundquist, research on HIV can be compared to a series of successive marathons. During the first marathon, the research community strove to develop effective treatments for the virus. After nearly three decades, they are nearing that finish line, but the next marathon is now underway — to develop a vaccine or a cure for HIV.
"In order to develop a vaccine and cure people who have HIV, we have to understand the vulnerabilities of the virus," Sundquist said. "With this funding, we can do just that at the structural and molecular level."
In 2007, U of U Health received initial funding to open the CHEETAH Center, which maintains the infrastructure, capacity and interdisciplinary knowledge to expand on the complex nature of the HIV virus. The researchers received a renewal grant in 2012 to continue their research.
Watch a video of the HIV virus exit a cell.
U of U Health scientists working with Sundquist include Debbie Eckert, Ph.D.; Nels Elde, Ph.D.; Chris Hill, D.Phil.; Janet Iwasa, Ph.D. and Michael Kay, M.D., Ph.D. In addition, the extramural research group includes Pamela Bjorkman, Ph.D. and Grant Jensen, Ph.D. from California Institute of Technology, Adam Frost, M.D., Ph.D. at University of California, San Francisco, Tom Hope, Ph.D. at Northwestern University, Neil King, Ph.D. at University of Washington, Tony Kossiakoff, Ph.D. and Gregory Voth, Ph.D. at University of Chicago, Walther Mothes, Ph.D. at Yale University, Joseph Puglisi, Ph.D. and Elisabetta Viani Puglisi, Ph.D. at Stanford University and Barbie Ganser-Pornillos, Ph.D. and Mark Yeager, M.D., Ph.D. at University of Virginia.