Transfer of HIV Between T Cells Captured on Video
A team of researchers from Mount Sinai and UC Davis have for the first time captured on video the transfer of HIV from infected to uninfected T cells through structures called virological synapses.
A team of researchers at Mount Sinai School of Medicine and the UC Davis Center for Biophotonics Science and Technology have for the first time captured on video the transfer of human immunodeficiency virus (HIV) from infected to uninfected T cells through structures called virological synapses. The breakthrough study, which could lead to new methods to block the transmission of HIV, will be published in the March 27 edition of Science.
Most prior studies of HIV dissemination have focused on free roaming viruses, but this study shows us how direct T cell-to-T cell contact could in fact be the predominant mode of dissemination within the body, said Dr. Benjamin Chen, Assistant Professor of Medicine, Infectious Diseases, Mount Sinai School of Medicine.
Direct T cell-to-T cell transfer through virological synapses is a highly efficient avenue of HIV infection. Our recent experiments show that the viral structural protein moves with surprising speed in infected cells and that the cell machinery actively participates in the transport of virus between T cells. This suggests there are many targets for interfering with the process, said Dr. Chen.
In order to make the HIV virus visible to track on video from cell to cell, researchers at Mount Sinai created a molecular clone of infectious HIV that contains green fluorescent jellyfish protein. With the team at UC Davis, they then used quantitative, high-speed 3D video microscopy to record both viral particle formation and transmission of the virus between T cells.
The resulting images and videos show that, once an infected cell adheres to a healthy cell, the HIV proteins – which appear bright green in the study – migrate within minutes to the contact site. At that point, large packets of virus are simultaneously released by the infected cell and internalized by the recipient cell. This efficient mode of transfer is a distinct pathway from the cell-free infection that has been the focus of most prior HIV studies, and reveals another mechanism by which the virus evades immune responses that can neutralize free virus particles within the body.
We found that the transfer of HIV is highly coordinated between T cells, and that the transfer is rapid and massive, said Dr. Chen. "Future efforts to block HIV transmission may be designed to specifically exploit and block this cell-to-cell mode of infection."
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation’s oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 50,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.
Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants.
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.