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.
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.


CONCLUSIONS
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.
Puigdomènech
Isabel
I
Fundació irsiCaixa, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Barcelona, Catalonia, Spain. ipuig@irsicaixa.es
Massanella
Marta
M
Izquierdo-Useros
Nuria
N
Ruiz-Hernandez
Raul
R
Curriu
Marta
M
Bofill
Margarita
M
Martinez-Picado
Javier
J
Juan
Manel
M
Clotet
Bonaventura
B
Blanco
Julià
J
D015703:Antigens, CD / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D006678:HIV / Q000254:growth & development*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D011485:Protein Binding
D015703:Antigens, CD; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; C483616:ICAM3 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1