Understanding HIV: How cell-to-cell virus transmission occurs in lymphoid tissues
During cell-to-cell transmission, HIV-1-infected T cells form stable contacts with uninfected T cells and massively transfer newly formed virus particles via these contacts. Cell-to-cell virus transmission is much more efficient than infection by cell-free viruses. It also allows HIV-1 to evade antiviral drugs, potentially contributing to maintenance of virus reservoirs during antiviral therapy.
In lymphoid organs where cell-to-cell transmission likely occurs frequently, stroma cells and extracellular matrices (ECMs) regulate T cell behaviors physically and chemically in the 3-dimensional space. However, mechanistic studies of cell-to-cell transmission have relied on simple cocultures of infected and uninfected T cells, and therefore effects of lymphoid organ components and architectures have not been addressed. Here we will reconstitute the lymphoid-organ-like environment using 3-dimensional scaffolds and examine the effects of stroma cells, ECMs, and the 3-dimensionality on cell-to-cell HIV transmission. We will also corroborate these studies with analyses of virus spread in lymphoid tissues ex vivo.
Secondary lymphoid organ fibroblastic reticular cells mediate trans-infection of HIV-1 via CD44-hyaluronan interactions
Article published in Nature Communications journal.
$410,895 grant from the National Institutes of Health
Characterizing natural hydrogel for reconstruction of three-dimensional lymphoid stromal network to model T-cell interactions
Published in Journal of Biomedical Materials Research Part A