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Numerous viruses manipulate host factors for viral production. We demonstrated that human enterovirus A71 (EVA71), a primary causative agent for hand, foot, and mouth disease (HFMD), increased the level of the DNA damage response (DDR) marker γ-H2AX. DDR is primarily mediated by the ataxia telangiectasia mutated (ATM), ATM and Rad3-related (ATR), or DNA-dependent protein kinase (DNA-PK) pathways. Upregulation of γ-H2AX by EVA71 was dependent on the ATR but not the ATM or DNA-PK pathway. As a nuclear factor, there is no previous evidence of cytoplasmic distribution of γ-H2AX. However, the present findings demonstrated that EVA71 encouraged the localization of γ-H2AX to the cytoplasm. Of note, γ-H2AX formed a complex with structural protein VP3, non-structural protein 3D, and the viral genome. Treatment with an inhibitor or CRISPR/Cas9 technology to decrease or silence the expression of γ-H2AX decreased viral genome replication in host cells; this effect was accompanied by decreased viral protein expression and virions. In animal experiments, caffeine was used to inhibit DDR; the results revealed that caffeine protected neonatal mice from death after infection with EVA71, laying the foundation for new therapeutic applications of caffeine. More importantly, in children with HFMD, γ-H2AX was upregulated in peripheral blood lymphocytes. The consistent in vitro and in vivo data on γ-H2AX from this study suggested that caffeine or other inhibitors of DDR might be novel therapeutic agents for HFMD.

Eight members of a big family with laboratory-confirmed COVID-19 pneumonia were admitted to First Hospital of Jilin University, Changchun, China, from 28 January to 5 February 2020. The clinical records, laboratory results, and chest computed tomography (CT) scans were retrospectively reviewed. Throat swab samples were positive for severe acute respiratory syndrome coronavirus 2, confirmed by the Center for Disease Control and Prevention of Changchun. All eight patients had fever of different degrees; and 6, 3, and 2 had cough; diarrhea; and sore throat. With disease progression, the percentage of lymphocytes in older patients increased, CT images worsened, and the ratio of lymphocytes increased when images revealed inflammation absorption. Although the CT images showed ground-glass opacities in the youngest patient, his lymphocyte count did not decrease with mild clinical symptoms, and the images showed that inflammation was quickly absorbed. Only the oldest patient developed critical illness. The C reaction protein (CRP) levels of Patient 5 increased significantly, and the rate of decline was the slowest, while his condition was the most severe. The clinical manifestations of COVID-19 in this family cluster varied with contact, age, and underlying disease. Lymphocyte count and quality of chest CT images appeared inversely associated with disease severity. CRP changes may be an indicator of disease severity and prognosis.