An integrin/MFG-E8 shuttle loads HIV-1 viral-like particles onto follicular dendritic cells in mouse lymph node.

ABSTRACT: During human immunodeficiency virus-1 (HIV-1) infection lymphoid organ follicular dendritic cells (FDCs) serve as a reservoir for infectious virus and an obstacle to curative therapies. Here, we identify a subset of lymphoid organ sinus lining macrophage (SMs) that provide a cell-cell contact portal, which facilitates the uptake of HIV-1 viral-like particles (VLPs) by FDCs and B cells in mouse lymph node. Central for portal function is the bridging glycoprotein MFG-E8. Using a phosphatidylserine binding domain and an RGD motif, MFG-E8 helps target HIV-1 VLPs to ?v integrin bearing SMs. Lack of MFG-E8 or integrin blockade severely limits HIV-1 VLP spread onto FDC networks. Direct SM-FDC virion transfer also depends upon short-lived FDC network abutment, likely triggered by SCSM antigen uptake. This provides a mechanism for rapid FDC loading broadening the opportunity for rare, antigen reactive follicular B cells to acquire antigen, and a means for HIV virions to accumulate on the FDC network.

SUBMITTER: Park C 

PROVIDER: S-EPMC6901335 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature