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

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

eLife (2019-12-04)
Chung Park, John H Kehrl
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 αv 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.

MATERIALS
Product Number
Brand
Product Description

Avanti
18:1-06:0 NBD PC, Avanti Research - A Croda Brand
Avanti
18:1-06:0 NBD PC, Avanti Research - A Croda Brand 810132C
Sigma-Aldrich
Triton X-100, laboratory grade
Avanti
18:1 (Δ9-Cis) PC (DOPC), Avanti Research - A Croda Brand
Avanti
18:1 (Δ9-Cis) PC (DOPC), Avanti Research - A Croda Brand