Sooty mangabeys, a type of African monkey, have intrigued scientists for years because they can survive infection by SIV, a relative of HIV, and not succumb to AIDS.
Researchers have identified a way some of sooty mangabeys' immune cells resist infection: they close the gates that SIV and HIV use to get into the cell. The findings may lead to strategies to help HIV-infected individuals cope better with infection.
The results are published online in the journal Nature Medicine.
"We have shown sooty mangabeys can prevent SIV from infecting a very important part of the immune system," says first author Mirko Paiardini, PhD, senior research scientist at Yerkes National Primate Research Center, Emory University. "This protection from infection comes from reducing the levels on the cell surface of a molecule that SIV uses to enter the cell."
Co-first author is postdoctoral fellow Barbara Cervasi. The senior author is Guido Silvestri, MD, chief of microbiology and immunology at Yerkes National Primate Research Center, Emory University. Collaborators included investigators from NIH, University of Pennsylvania, University of Pittsburgh and University Hospital Ulm.
To infect a cell, HIV and SIV need to find two molecules on the cell's surface. Scientists call these molecules co-receptors, and they can be thought of as gates. One of the co-receptors is CD4, which appears on immune cells called T cells. The other is called CCR5. Stimulating a T cell usually increases the level of CCR5, facilitating infection.
Paiardini, Cervasi and their colleagues found that in sooty mangabeys, a type of T cell called a central memory T cell doesn't turn on CCR5. This means that even when a sooty mangabey is infected with SIV, some T cells can mostly avoid being killed by the virus.
Memory T cells help the immune system respond to an infection faster and stronger the second time around. Central memory T cells are long-lived and found in lymph nodes, in contrast to effector memory T cells, which have shorter life spans and are found mostly in tissues, such as the intestines, Paiardini says.
"Not all T cells are created equal," he says. "Some appear to be more important than others for keeping the immune system up and running. This is why having central memory T cells resistant to infection is so valuable. By protecting central memory T cells, sooty mangabeys avoid the loss of T cells and the chronic immune activation that are the hallmarks of AIDS in humans."
Scientists have identified several differences in the pattern of infection between sooty mangabeys and both humans and rhesus macaques, a monkey that is susceptible to SIV infection.
"For several years, we and others thought lack of chronic immune activation was the main factor protecting sooty mangabeys from AIDS," Paiardini says. "This study changes this working model and proposes that lack of immune activation in sooty mangabey is secondary, deriving from their ability to protect and maintain their central memory T cells."
Paiardini continues, "We would have not been able to perform such complex comparative studies without the presence of the large colony of sooty mangabeys at the Yerkes National Primate Research Center."
The National Institutes of Health supported this research.
For eight decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve the health and well-being of humans and nonhuman primates. Today, the center, as one of only eight National Institutes of Health–funded national primate research centers, provides leadership, training and resources to foster scientific creativity, collaboration and discoveries. Yerkes-based research 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; treat drug addiction; interpret brain activity through imaging; increase understanding of progressive illnesses such as Alzheimer's and Parkinson's diseases; unlock the secrets of memory; determine how the interaction between genetics and society shape who we are; and advance 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.
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