Cell type-dependent retention and transmission of HIV-1 by DC-SIGN

Abstract

DC‐SIGN (CD209) is a C‐type lectin expressed by several groups of dendritic cells (DC), including those derived from blood monocytes and DC found beneath genital epithelium. DC‐SIGN binds the envelope glycoprotein of HIV‐1 and facilitates transmission of infectious virus to permissive CD4+ T cells. We have compared the capacity of DC‐SIGN in different cell types to bind, retain and transmit infectious HIV‐1 to T cells. The analyzed cells included monocyte‐derived DC, and three different DC‐SIGN‐expressing transfectants termed THP, 293 and HOS. Our results show that DC‐SIGN transfectants were able to bind HIV‐1 virions comparably to DC. However, only the THP monocytic cell line shared with DC the capacity to retain for several days virus that was infectious for T cells. In both THP‐DC‐SIGN transfectants and DC, but not in 293 cells, HIV‐1 was localized to intracellular compartments that did not double label for endosomal and lysosomal markers or for DC‐SIGN itself. Virus remained detectable in these compartments for at least 2 days. Anti‐DC‐SIGN antibodies blocked the binding and transmission of HIV‐1 in DC‐SIGN transfectants, as monitored by PCR for HIV LTR/gag and p24 ELISA. However anti‐DC‐SIGN antibodies did not block virus binding and transmission to T cells as well in DC as in THP‐DC‐SIGN transfectants. Thus, the function of DC‐SIGN in HIV‐1 transmission depends on its cellular context, since only DC and the THP monocyte cell line, but not 293 and HOS, are able to use DC‐SIGN to retain HIV‐1 in a highly infectious state for several days.