DISTINCT EFFECTS OF HUMAN HERPESVIRUS 6 AND HUMAN HERPESVIRUS-7 ON SURFACE-MOLECULE EXPRESSION AND FUNCTION OF CD4+ T-CELLS

This study was undertaken to investigate the effects of newly isolated T lymphotropic viruses, human herpesvirus (HHV)-6 and HHV-7, on CD4(+) T cells. We first examined changes in surface molecule expression on CD4(+) T cells after infection with HHV-6 or HHV-7 by flow cytometry. Among surface molecules examined, CD3 expression appeared to decline markedly after infection with HHV-6 variant A (strain U1102) but the decreased level of CD3 expression after infection with HHV-6 variant B (strain Z29) was slight. Impairment of surface CD3 expression on HHV-6 variant A-infected cells was also demonstrated by measuring intracellular free Ca2+ concentration in response to anti-CD3 mAb. In contrast, HHV-7 infection induced a marked loss of surface CD4 expression, but the decline of CD3 expression was slight. Cytotoxic activity of virus-specific CD4(+) CTL clones decreased after infection with both HHV-6 variant A or HHV-7 but the degree of reduction of cytotoxicity by HHV-6 variant B was not significant. Addition of lectin restored the cytotoxicity of HHV-7-infected CTL but not that of HHV-6 variant A-infected CTL. Northern blot analysis and immunoprecipitation showed that infection with HHV-6 and HHV-7 did not affect the transcription and protein synthesis of CD3 and CD4. These findings suggest that both HHV-6 and HHV-7 may directly cause T cell immunodeficiency but that the mechanisms of CD4(+) T cell dysfunction mediated by HHV-6 and HHV-7 are different.