Interleukin-10 (IL-10) is an inhibitory cytokine produced by various cell types. It exhibits strong sequence homology to BCRF-1 (viral IL-10, vIL-10), an open reading frame in the Epstein-Barr-virus (EBV) genome. Using in situ hybridization (ISH), polymerase chain reaction (PCR) and immunohistochemistry, we checked 41 cases of nasopharyngeal carcinoma (NPC), to study the presence of EBV in the tumor cells, as well as to clarify the relationship between IL-10 expression of the tumor cells and the response of cytotoxic T cells. IL-10 expression was studied by immunohistochemistry; as a result, 29 of 41 cases expressed EBER-1 RNA of EBV by ISH. In addition, 19 of the 29 with EBV and 9 of 12 without EBV cases expressed IL-10 in the tumor cells. The number of cytotoxic T cells increased in the tumor tissue, and the increase in the intratumoral stroma was stronger than in the remaining normal epithelia. The number of cytotoxic T cells also significantly increased in the cases with EBV. On the other hand, in the IL-10-positive series, the number of cytotoxic T cells decreased significantly more than in IL-10-negative series. In view of the established inhibitory effects of IL-10, expression of IL-10 may therefore be one of the mechanisms for NPC cells as well as EBV to counter local immune defense. However, we could not conclude whether or not IL-10 expression was directly induced by EBV.
Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviruses and indicate that remdesivir is a promising antiviral treatment for EV71 and other enterovirus infections.
Hantaviruses, etiologic pathogens responsible for two severe human diseases, exist in areas ranging from Eurasia to America and remain global public health concerns. Conventionally, plaque formation assays have been used for hantavirus titering. However, hantaviruses replicate slowly within cells and produce minimal cytopathic effects, making this technique difficult to master. The improved enzyme-linked immunosorbent assay-based antigen detection method is easier to perform but is still time consuming. Here, we established an enzyme-linked focus formation assay (FFA) for Hantaan virus titering that is twice as fast as traditional assays. Moreover, using this method, we evaluated the effects of favipiravir (T-705) and another influenza virus drug, baloxavir acid (BXA), on hantavirus replication. We found that the endonuclease inhibitor BXA exerted similar anti-hantavirus effects as T-705. Overall, we developed a time-saving method for hantavirus titering and suggest BXA as a potential treatment choice for hantavirus-exposed individuals.
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