Comparative study of herpes simplex virus receptor expression on human lymphoid cells

Lymphocytes represent key cells of the immune system and play an important role against viral infections. However, the expression and quantification of virus receptors on lymphoid cells have, in most cases, not been studied. We report here a study of the expression of herpes simplex virus (HSV) receptors by different human lymphoid cell types. Using flow cytometry and fluorescein isothiocyanate-conjugated HSV1 (F-HSV1) we analyzed virus binding to fresh and mitogen-stimulated B and T lymphocytes and established monoclonal lymphoid cell lines (LCL). The study included analysis of (a) virus binding in relation to cell size; (b) specificity of the virus binding using virus-specific monoclonal and polyclonal antibodies as well as heparin, an inhibitor of HSV attachment to cells; and (c) HSV1 receptor density on various targets. The results show that HSV1 binds to all the cell types tested, including some cell lines which were found negative for virus replication. This binding was specifically inhibited with either purified human anti-HSV1 F(ab)'2 or heparin. Stimulation of peripheral blood leukocytes with phytohemagglutinin resulted in a remarkable increase of receptor density on T lymphocytes. B cells showed an increase in receptor density only following PBL stimulation with pokeweed mitogen. The density of HSV1 receptor on fresh T and B lymphocytes is significantly lower than that on mitogen-stimulated cells and LCL; this indicates that mitogenic activation or transformation of lymphocytes leads to an upregulation of the expression of cellular receptors for HSV1 and may in turn explain why HSV replicates only in stimulated and not in resting fresh lymphocytes.