Modulation of the Host Environment by Human Cytomegalovirus with Viral Interleukin 10 in Peripheral Blood

• Published in: The Journal of infectious diseases Vol. 215; no. 6; pp. 874 - 882
• Main Authors: Young, Vivian P., Mariano, Margarette C., Tu, Carolyn C., Allaire, Kathryn M., Avdic, Selmir, Slobedman, Barry, Spencer, Juliet V.
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15.03.2017
• Subjects: Antibodies, Viral - blood; Cross Reactions; Cytomegalovirus - immunology; Cytomegalovirus Infections - blood; Cytomegalovirus Infections - immunology; Enzyme-Linked Immunosorbent Assay; Healthy Volunteers; Humans; Immune Tolerance; Immunoglobulin G - blood; Immunoglobulin M - blood; Interleukin-10 - blood; Interleukin-10 - immunology; Major; Monocytes - immunology; Viral Proteins - blood; Viral Proteins - immunology; Virus Latency; VIRUSES; vIL-10; viral cytokine; cmvIL-10; cytomegalovirus; CMV; interleukin 10
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jix043

Background. Human cytomegalovirus (HCMV) is a herpesvirus with both lytic and latent life cycles. Human cytomegalovirus encodes 2 viral cytokines that are orthologs of human cellular interleukin 10 (cIL-10). Both cytomegalovirus interleukin 10 (cmvIL-10) and Latency-associated cytomegalovirus interleukin 10 (LAcmvIL-10) (collectively vIL-10) are expressed during lytic infection and cause immunosuppressive effects that impede virus clearance. LAcmvIL-10 is also expressed during latent infection of myeloid progenitor cells and monocytes and facilitates persistence. Here, we investigated whether vIL-10 could be detected during natural infection. Methods. Plasma from healthy blood donors was tested by enzyme-linked immunosorbent assay for anti-HCMV immunoglobulin G and immunoglobulin M and for cIL-10 and vIL-10 levels using a novel vIL-10 assay that detects cmvIL-10 and LAcmvIL-10, with no cross-reactivity to cIL-10. Results. vIL-10 was evident in HCMV+ donors (n = 19 of 26), at levels ranging 31-547 pg/mL. By comparison, cIL-10 was detected at lower levels ranging 3-69 pg/mL. There was a strong correlation between vIL-10 and cIL-10 levels (P = .01). Antibodies against vIL-10 were also detected and neutralized vIL-10 activity. Conclusions. vIL-10 was detected in peripheral blood of healthy blood donors. These findings suggest that vIL-10 may play a key role in sensing or modifying the host environment during latency and, therefore, may be a potential target for intervention strategies.