ICAM-3 influences human immunodeficiency virus type 1 replication in CD4+ T cells independent of DC-SIGN-mediated transmission

Abstract

We investigated the role of ICAM-3 in DC-SIGN-mediated human immunodeficiency virus (HIV) infection of CD4(+) T cells. Our results demonstrate that ICAM-3 does not appear to play a role in DC-SIGN-mediated infection of CD4(+) T cells as virus is transmitted equally to ICAM-3(+) or ICAM-3(-) Jurkat T cells. However, HIV-1 replication is enhanced in ICAM-3(-) cells, suggesting that ICAM-3 may limit HIV-1 replication. Similar results were obtained when SIV replication was examined in ICAM-3(+) and ICAM-3(-) CEMx174 cells. Furthermore, while ICAM-3 has been proposed to play a co-stimulatory role in T cell activation, DC-SIGN expression on antigen presenting cells did not enhance antigen-dependent activation of T cells. Together, these data indicate that while ICAM-3 may influence HIV-1 replication, it does so independent of DC-SIGN-mediated virus transmission or activation of CD4(+) T cells.

HIV-1 Gag Associates with Specific Uropod-Directed Microdomains in a Manner Dependent on Its MA Highly Basic Region

“…It is also of interest to determine why HIV-1 evolved to exclude ICAM-3 from the UDMs with which the virus associates. A previous study showed that HIV-1 replication in Jurkat T cells is inefficient when ICAM-3 is expressed and that ICAM-3 appears to exert the negative effect during the late phase of the virus replication cycle (101). Thus, it is tempting to speculate that reducing the ICAM-3 association with assembling viruses at the plasma membrane is potentially advantageous for HIV-1 assembly and/or the subsequent transmission.…”

HIV-1TransInfection of CD4+T Cells by Professional Antigen Presenting Cells

“…HIV-1 trans infection is impaired in MDDC from patients with leukocyte adhesion deficiency type 1 whose T cells lack expression of LFA-1 [ 244 ]. There are contradictory data, however, that not all LFA-1 ligands play this role, as ICAM-1 [ 243 ] and ICAM-3 [ 245 ] have not been confirmed to be involved in HIV-1 trans infection. However, additional evidence that such binding is important in trans infection is that it can be prevented by inhibitors that block the virus-cell fusion process, for example, CD4 attachment blockers (mAb), fusion blockers [T20], and chemokine receptor blockers (RANTES) [ 246 , 247 ].…”

Intercellular Adhesion Molecule 1 (ICAM-1), but Not ICAM-2 and -3, Is Important for Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission

“…It has been proposed that DC-SIGN-ICAM-3 interactions stabilize DC-T-cell adhesion and enhance HIV-1 transmission (16,32). However, ICAM-3 expression on target cell lines is not essential for DC-SIGN-mediated HIV-1 transmission (1,48). It remains unclear whether ICAM-3 expressed on primary CD4…”