Immunosuppressive effect of human herpesvirus 6 on T-cell functions: suppression of interleukin-2 synthesis and cell proliferation.
Human herpesvirus-6 (HHV-6), the etiologic agent of roseola, is ubiquitous, establishes latency in the host, and can infect a variety of immunocompetent cells, with CD4+ T lymphocytes being the targets in which it replicates most efficiently. The present study was undertaken to learn more about specific immunobiologic effects of HHV-6 infection on T-lymphocyte functions. Our data demonstrate that infection of peripheral blood mononuclear cells (PBMC) by HHV-6 results in suppression of T-lymphocyte functions, as evidenced by reduced interleukin-2 (IL-2) synthesis and cellular proliferation. In fact, HHV-6-infected PBMC secreted 50% less IL-2 than mock-infected cells after mitogenic stimulation with OKT3 antibody or phytohemmaglutinin (PHA). The inhibition of IL-2 by HHV-6 was also observed in enriched T-cell cultures, suggesting a direct effect of this virus on this cell type. Messenger RNA (mRNA) analysis by reverse-transcriptase polymerase chain reaction (PCR) indicated that HHV-6 diminishes IL-2 mRNA levels in mitogen-stimulated peripheral blood T cells. These results were also confirmed by Northern blot using the leukemic T-cell line Jurkat. This inhibitory effect of HHV-6 did not require infectious virus, as the use of UV-irradiated HHV-6 produced similar results. Moreover, HHV-6-infected PBMC showed up to an 85% reduction in their mitogen-driven proliferative response, as compared with sham-infected cells. Proliferation of both CD4+ and CD8+ T cells was affected by HHV-6. Taken together, our data show that infection of T cells by HHV-6 results in immune suppression characterized by a downregulation of IL-2 mRNA and protein synthesis accompanied by diminished cellular proliferation.
Laboratory of Immunovirology, Sainte Justine Hospital, Québec, Canada.
L
L
Flamand
J
J
Gosselin
I
I
Stefanescu
D
D
Ablashi
J
J
Menezes
D001483:Base Sequence; D002455:Cell Division; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology*; D014158:Transcription, Genetic
D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger