HIV transfer between CD4 T cells does not require LFA-1 binding to ICAM-1 and is governed by the interaction of HIV envelope glycoprotein with CD4.

Abstract

BACKGROUND:

Cell-to-cell HIV transmission requires cellular contacts that may be in part mediated by the integrin leukocyte function antigen (LFA)-1 and its ligands intercellular adhesion molecule (ICAM)-1, -2 and -3. The role of these molecules in free virus infection of CD4 T cells or in transinfection mediated by dendritic cells (DC) has been previously described. Here, we evaluate their role in viral transmission between different HIV producing cells and primary CD4 T cells.

RESULTS:

The formation of cellular conjugates and subsequent HIV transmission between productively infected MOLT cell lines and primary CD4 T cells was not inhibited by a panel of blocking antibodies against ICAM-1, ICAM-3 and alpha and beta chains of LFA-1. Complete abrogation of HIV transmission and formation of cellular conjugates was only observed when gp120/CD4 interactions were blocked. The dispensable role of LFA-1 in HIV transmission was confirmed using non-lymphoid 293T cells, lacking the expression of adhesion molecules, as HIV producing cells. Moreover, HIV transmission between infected and uninfected primary CD4 T cells was abrogated by inhibitors of gp120 binding to CD4 but was not inhibited by blocking LFA-1 binding to ICAM-1 or ICAM-3. Rather, LFA-1 and ICAM-3 mAbs enhanced HIV transfer. All HIV producing cells (including 293T cells) transferred HIV particles more efficiently to memory than to naive CD4 T cells.

CONCLUSION:

In contrast to other mechanisms of viral spread, HIV transmission between infected and uninfected T cells efficiently occurs in the absence of adhesion molecules. Thus, gp120/CD4 interactions are the main driving force of the formation of cellular contacts between infected and uninfected CD4 T cells whereby HIV transmission occurs.

• Authors: Isabel Puigdomènech, Marta Massanella, Nuria Izquierdo-Useros, Raul Ruiz-Hernandez, Marta Curriu, Margarita Bofill, Javier Martinez-Picado, Manel Juan, Bonaventura Clotet, Julià Blanco
• Journal: Retrovirology (Retrovirology) Vol. 5 Pg. 32 (Mar 31 2008) ISSN: 1742-4690 [Electronic] England
• PMID: 18377648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• CD4 Antigens
• Cell Adhesion Molecules
• HIV Envelope Protein gp120
• ICAM3 protein, human
• Lymphocyte Function-Associated Antigen-1
• Intercellular Adhesion Molecule-1

Topics

• Antigens, CD (metabolism)
• CD4 Antigens (metabolism)
• CD4-Positive T-Lymphocytes (virology)
• Cell Adhesion Molecules (metabolism)
• Cell Line
• Cells, Cultured
• HIV (growth & development)
• HIV Envelope Protein gp120 (metabolism)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Lymphocyte Function-Associated Antigen-1 (metabolism)
• Protein Binding