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

<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background.</div>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.<div class="boxTitle">Methods.</div>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.<div class="boxTitle">Results.</div>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 (<span style="font-style:italic;">P</span> = .01). Antibodies against vIL-10 were also detected and neutralized vIL-10 activity.<div class="boxTitle">Conclusions.</div>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.</span>

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