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Immune Modulatory Function of Human Cytomegalovirus-Encoded UL128 in the Pathogenesis of Infection Related Hearing Loss

Zheng Qi, Tao R, Gao H, Xu J, Sun Y, Zhao N, Gu W and Shang S

Inflammatory cytokines such as tumor necrosis factor (TNF)-a, interleukin (IL)-6 were supposed to participate in the tissue damage of human cytomegalovirus (HCMV) infection related diseases. The pathogenesis of HCMV associated hearing loss is poorly understood mainly due to the lack of applicable virus infected model. We subjected cochlear epithelial cell line derived from human auditory progenitors to HCMV infection and examined the levels of cytokines released in the co-cultural supernatant of peripheral blood monocytes and HCMV pre-infected cochlear epithelial cells. Human cochlear epithelial cell line cultured in vitro is replicable and permissive for HCMV productive infection. Detection of the co-culture system revealed up-regulation of cytokines including IL-6 and TNF-α. Since HCMV UL128 protein interferes with virus entry into epithelial cells as well as eliciting primary antibody in vivo, transcription of HCMV UL128 gene was suppressed by short interference RNA in this experiment. Cytokine analysis revealed that UL128 deficient HCMV got impairment of inducing IL-6 and TNF-α production when interacted with host immune cells. We deduce that UL128 may serve as a viral immune modulator participating in the pathology of HCMV related hearing loss and UL128 gene can be a potential target for treatment of infection induced immune pathological damage.