Human hepatoma cells transmit surface bound HIV-1 to CD4+ T cells through an ICAM-1/LFA-1-dependent mechanism

Abstract

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. 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. 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.