Human hepatoma cells transmit surface bound HIV-1 to CD4+ T cells through an ICAM-1/LFA-1-dependent mechanism.
BACKGROUND
During the viremic phase of human immunodeficiency virus type-1 (HIV-1) infection, hepatocytes are likely to be constantly exposed to circulating virions. Knowing that a contact between hepatocytes and CD4+ T lymphocytes is favoured by the local slow blood flow present within the liver, we hypothesize that hepatic cells can act as a viral reservoir and thus contribute to HIV-1 propagation.


RESULTS
We report that human hepatoma cells bind and internalize HIV-1 particles. Infection of CD4+ T cells was found to be much more efficient following a contact with virus-loaded hepatocytes than with cell-free virus. Additional studies suggest that infection of CD4+ T cells in trans with hepatocytes carrying virus is primarily due to surface bound HIV-1 particles and relies on LFA-1/ICAM-1 interactions.


CONCLUSIONS
This work represents the first demonstration by which circulating CD4+ T cells can be potentially infected with HIV-1 through a contact with hepatocytes in the liver.
Fromentin
Rémi
R
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Faculté de Médecine, Université Laval, Québec, Canada. remi.fromentin@crchul.ulaval.ca
Tardif
Mélanie R
MR
Tremblay
Michel J
MJ
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D006528:Carcinoma, Hepatocellular / Q000821:virology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000821:virology; D005434:Flow Cytometry; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism / Q000502:physiology*
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1