Cellular Mechanisms of HIV-1 Dissemination Elucidated
Mice study shows HIV-1 infected T cells play key role in local transmission, subsequent spread
THURSDAY, Aug. 2 (HealthDay News) -- HIV-1-infected T cells are motile, form syncytia, and play a key role in HIV dissemination, according to a letter to the editor published online Aug. 1 in Nature.
Thomas T. Murooka, Ph.D., from Harvard Medical School in Boston, and colleagues investigated whether the T-cell contacts observed in in vitro studies were sufficiently stable to allow for functional synapse formation in vivo in epithelial and lymphoid tissues. Multiphoton intravital microscopy was used to examine the dynamic behavior of HIV T cells in the lymph nodes of humanized mice.
The researchers found that productively infected T cells were evenly distributed throughout the lymph node cortex as a result of the robust migration of most cells. Multinucleated syncytia were formed by a subset of infected cells, via cell fusion, which was dependent on the HIV envelope. Cell length was increased up to 10 times that of migrating uninfected T cells by formation of long membrane tethers, which resulted from both dyssynchronous motility of syncytia and adhesion to CD4+ lymph node cells. Interruption of T-cell recirculation by blocking the exit of migratory T cells from the lymph nodes into efferent lymph vessels correlated with limited HIV dissemination and strongly reduced plasma viremia.
"We have found that HIV-infected T cells are motile, form syncytia and establish tethering interactions that may facilitate cell-to-cell transmission through virological synapses," the authors write. "T-cell migration in lymph nodes spreads infection locally, and their recirculation through tissues is important for efficient systemic viral spread, suggesting new molecular targets to antagonize HIV infection."