ATLANTA--Researchers at Emory University School of Medicine and Children’s Healthcare of Atlanta have made a leap forward in understanding how HIV “gets dressed” in the human cells it has taken over.
Without its clothes – the envelope proteins that appear on the surface of the viral particle -- the virus can’t spread from one cell to another, says lead researcher Paul Spearman, MD.
Spearman is chief research officer for Children's Healthcare of Atlanta and Nahmias-Schinazi Professor and vice chair of research in the Department of Pediatrics, Emory School of Medicine.
The finding could potentially lead to new antiretroviral drugs that would force HIV to make “naked” particles and be non-infectious.
The results are published in the journal PLOS Pathogens. The first author is postdoctoral fellow Mingli Qi, PhD. Emory and Children’s investigators collaborated with the laboratory of James Goldenring, MD, PhD at Vanderbilt University School of Medicine.
The team has identified a pair of human proteins, FIP1c and Rab14, which are needed for sorting and processing the envelope protein before viral assembly. Normally, uninfected cells use FIP1c and Rab14 to sort a variety of newly produced proteins before displaying them on their surfaces.
“This helps us better understand not only HIV, but many other viruses, and how they take over the cell’s sorting and recycling machinery to build their own structures,” Spearman says.
Another impact of the discovery could be in helping to decode HIV’s stealthiness. HIV is unlike a lot of other viruses in that HIV particles have a limited number of envelope proteins. While the envelope protein is an essential tool the virus uses to enter and infect white blood cells, the sparse presentation is thought to help HIV avoid the immune system and may explain why some HIV vaccines have been ineffective.
Scientists already knew that part of the envelope protein, its “tail”, keeps the particles from becoming crowded. It appears that FIP1c and Rab14 grab this tail when the viral particles are being assembled, Spearman says.
“It has been a mystery for many years how HIV controls incorporation of the envelope protein into the virion, and we have worked the past four years to figure this out,” he says.
“We are trying to turn these findings to our advantage,” he adds. “Using this knowledge, we are designing vaccines with virus-like particles that are stuffed with more envelope protein than HIV normally has, and thus could be more likely to stimulate antibodies.”
The research was supported by the National Institute of Allergy and Infectious Diseases (AI40338 and P30 AI050409), the National Institute of Diabetes and Digestive and Kidney Diseases (DK48370), and the James B. Pendleton Charitable Trust.
Reference: M. Qi et al. Rab11-FIP1C and Rab14 Direct Plasma Membrane 1
Sorting and Particle Incorporation of the HIV-1 Envelope Glycoprotein Complex
PLOS Path (2013).
NOTE: We could illustrate with a diagram like this:
About Children’s Healthcare of Atlanta
Children’s Healthcare of Atlanta, a not-for-profit organization, is committed to enhancing the lives of children through excellence in patient care, research and education. Managing more than half a million patient visits annually at three hospitals and 20 neighborhood locations, Children’s is one of the largest clinical care providers for children in the country. Children’s offers access to more than 30 pediatric specialties and is ranked among the top children’s hospitals by Parents magazine and U.S.News & World Report. With generous philanthropic and volunteer support, Children’s has made an impact in the lives of children in Georgia, the United States and throughout the world.
About the Robert W. Woodruff Health Sciences Center of Emory University
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include schools of medicine, nursing, and public health; Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia.