Scientists find clues to how HIV 'gets dressed'
Woodruff Health Sciences Center | April 11, 2013
HIV particles have a limited number of envelope proteins (here they look like green clovers). 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. Image courtesy of NIAID.
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.Qi led the team in identifying a pair of human proteins, FIP1c and Rab14, that 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 Institutes of Allergy and Infectious Diseases (AI40338 and P30 AI050409), the National Institutes 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).