Macrophages transmit human immunodeficiency virus type 1 products to CD4-negative cells: involvement of matrix metalloproteinase 9.
It was previously reported that human immunodeficiency virus type 1 (HIV-1) spreads in CD4 lymphocytes through cell-to-cell transmission. Here we report that HIV-1-infected macrophages, but not lymphocytes, transmit HIV-1 products to CD4-negative cells of either epithelial, neuronal, or endothelial origin in the absence of overt HIV-1 infection. This phenomenon was detectable as early as 1 h after the start of cocultivation and depended on cell-to-cell contact but not on the release of viral particles from donor cells. Transfer of HIV-1 products occurred upon their polarization and colocalization within zones of cell-to-cell contact similar to virological synapses. Neither HIV-1 Env nor Nef expression was required but, interestingly, we found that an HIV-1-dependent increase in matrix metalloproteinase 9 production from donor cells significantly contributed to the cell-to-cell transmission of the viral products. The macrophage-driven transfer of HIV-1 products to diverse CD4-negative cell types may have a significant role in AIDS pathogenesis.
Muratori
Claudia
C
Division of Pathogenesis of Retroviruses, National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
Sistigu
Antonella
A
Ruggiero
Eliana
E
Falchi
Mario
M
Bacigalupo
Ilaria
I
Palladino
Clelia
C
Toschi
Elena
E
Federico
Maurizio
M
D001253:Astrocytes / Q000821:virology; D002460:Cell Line; D042783:Endothelial Cells / Q000821:virology; D004847:Epithelial Cells / Q000821:virology; D005434:Flow Cytometry; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D014764:Viral Proteins / Q000378:metabolism*
D014764:Viral Proteins; D020780:Matrix Metalloproteinase 9