Modulatory effects of Epstein-Barr, herpes simplex, and human herpes-6 viral infections and coinfections on cytokine synthesis. A comparative study

• Published in: The Journal of immunology (1950) Vol. 149; no. 1; pp. 181 - 187
• Main Authors: Gosselin, J, Flamand, L, D'Addario, M, Hiscott, J, Stefanescu, I, Ablashi, DV, Gallo, RC, Menezes, J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.07.1992; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Base Sequence; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Herpes Simplex - immunology; Herpesviridae Infections - immunology; Herpesvirus 4, Human - immunology; Herpesvirus 6, Human - immunology; Humans; Immunobiology; In Vitro Techniques; Interleukin-1 - biosynthesis; Interleukin-1 - genetics; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - microbiology; Lymphokines, interleukins ( function, expression); Molecular Sequence Data; Oligodeoxyribonucleotides - chemistry; Regulatory factors and their cellular receptors; RNA, Messenger - genetics; Simplexvirus - immunology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Tumor Virus Infections - immunology; Gammaherpesvirinae; Human; Immunomodulation; Herpesviridae; Alphaherpesvirinae; Cytokine; Herpes; Interleukin 1β; Biosynthesis; Epstein Barr virus; Host virus relation; Infection; Virus; Interleukin 6; Herpesvirus hominis 6; Viral disease; Herpesvirus hominis; Comparative study; Tumor necrosis factor α
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.149.1.181

Herpesviruses such as EBV, HSV, and human herpes virus-6 (HHV-6) have a marked tropism for cells of the immune system and therefore infection by these viruses may result in alterations of immune functions, leading at times to a state of immunosuppression. We report the results of a comparative study in which we found that EBV, HSV-1, and HHV-6 act differentially on the immune system with regard to their effect on the synthesis of IL-1 beta, IL-6, and TNF-alpha, i.e., three immunoregulatory cytokines mainly secreted by activated monocytes/macrophages. Using the polymerase chain reaction technique, analyses of the mRNA levels for each of the three monokines after viral infection indicated that the effect exerted by each of these herpesviruses on cytokine synthesis by human PBMC was detectable at the transcriptional level. Different amounts of IL-1 beta protein were detected in infected PBMC cultures, HHV-6 being the strongest IL-1 beta up-regulatory among these three herpesviruses. Spontaneous releases of IL-6 and TNF-alpha were found reduced after infection by HHV-6 and EBV, respectively. In comparison to EBV and HHV-6, HSV-1 proved to be a weak monokine enhancer. Results of coinfection studies indicated that virus-induced suppressive effects on cytokine synthesis are dominant. In fact, EBV inhibited TNF-alpha synthesis even in the presence of HHV-6, a strong up-regulator of TNF-alpha synthesis. Similarly, EBV was unable to stimulate IL-6 production in the presence of HHV-6. Viral structural component(s) appeared to be responsible for the up-regulation of IL-6 by both EBV and HSV-1, and of TNF-alpha by HSV-1. Taken together, our observations illustrate that herpesviruses can selectively regulate cytokine synthesis thereby disturbing immune homeostasis; this effect may favor pathogenic events, including the reactivation and/or spread of other infectious agents within the host.