October 31, 2014
Lisa, 404-727-7709, email@example.com
Where does HIV hide? Antiretroviral drugs can usually control the virus, but can’t completely eliminate it. So any strategy to eradicate HIV from the body has to take into account not only the main group of immune cells the virus targets, called CD4 or helper T cells, but other infected cells as well.
New research from Yerkes National Primate Research Center, Emory University, sheds light on the question of which cells support viral replication and persistence, and the answers have implications for future efforts to eliminate HIV from the body in human patients.
The results were published Oct. 30 in the journal PLOS Pathogens.
"Our results have implications for efforts to cure HIV," says lead author Mirko Paiardini, PhD, assistant professor of pathology and laboratory medicine at Emory University School of Medicine and Yerkes National Primate Research Center. "Our findings suggest that therapeutic strategies aimed at stimulating infected macrophages may facilitate viral elimination."
Researchers at Yerkes looked at what happens when rhesus macaques have CD4 T cells removed from their immune systems before infection by HIV’s cousin SIV. They found that another type of immune cell, called macrophages, then becomes heavily infected by SIV. Infected cells are present in lymph nodes, intestine and brain as well as in the blood.
However, the macrophages live shorter than expected based on previous research studies, which calls into question the idea that the macrophages could serve as a long-term hideout when someone is infected by HIV but receiving antiretroviral drugs.
"Among HIV researchers, there has been a lot of debate about the contribution of macrophages to the HIV reservoir," Paiardini says. "We show that in the absence of CD4 T cells, macrophages can be heavily infected by SIV, which supports a role for macrophages in viral infection. However, when infected at high levels, macrophages become short-lived cells in vivo, with an average lifespan of 1.3 days. Thus, if validated in the setting of HIV infection in humans, our data support a model in which macrophages do not constitute the long-lived reservoir (in order of weeks) that has been proposed."
The researchers also found evidence that in macaques with depleted CD4 T cells, SIV is infecting microglial cells in the brain, otherwise rarely seen.
Co-first authors were postdoctoral fellow Luca Micci, PhD and Robin Iriele from Yerkes and Xavier Alvarez from Tulane. Yerkes co-authors included Guido Silvestri, MD, and Cynthia Derdeyn, PhD, and collaborators from Tulane University, the National Cancer Institute and the University of New South Wales contributed to the paper.
The research was supported by the National Institute of Allergy and Infectious Diseases (R56AI087186, R01AI084836, P30AI50409) and the NIH Director’s Office of Research Infrastructure Programs (Primate Centers: P51OD11132 – formerly NCRR P51RR000165).
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.
In the fields of microbiology and immunology, infectious diseases, pharmacology and drug discovery, transplantation, neurologic and psychiatric diseases, as well as behavioral, cognitive and developmental neuroscience, Yerkes scientists use innovative experimental models and cutting-edge technologies to explore and test transformative concepts aimed at: preventing and treating viral diseases such as AIDS; designing novel vaccines for infectious diseases such as malaria and tuberculosis; enhancing the potential of organ transplantation and regenerative medicine; discovering new drugs and drug classes through high-throughput screening; defining the basic neurobiology and genetics of social behavior and developing new therapies for disorders such as autism and drug addiction; understanding the biology of neurodegenerative diseases, such Alzheimer’s and Parkinson’s diseases; and advancing knowledge about the evolutionary links between biology and behavior.
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 the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.