Zika virus (ZIKV) infection during pregnancy is linked to severe birth defects, but mother-to-fetus transmission routes are unknown. We infected different primary cell types from mid- and late-gestation placentas and explants from first-trimester chorionic villi with the prototype Ugandan and a recently-isolated Nicaraguan ZIKV strain. ZIKV infects primary human placental cells and explants – cytotrophoblasts, endothelial cells, fibroblasts and Hofbauer cells in chorionic villi and amniotic epithelial cells, and trophoblast progenitors in amniochorionic membranes expressing Axl, Tyro3 and/or TIM1 viral entry cofactors. ZIKV produced NS3 and E proteins and generated higher viral titers in amniotic epithelial cells from mid-gestation compared to late-gestation placentas. Duramycin, a peptide that binds phosphatidylethanolamine in enveloped virions and precludes TIM1 binding, reduced ZIKV infection in placental cells and explants. Our results suggest that ZIKV spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes, and targeting TIM1 could suppress infection at the uterine-placental interface.
The global spread of dengue virus (DENV) infections has increased viral genetic diversity, some of which appears associated with greater epidemic potential. The mechanisms governing viral fitness in epidemiological settings, however, remain poorly defined. We identified a determinant of fitness in a foreign dominant (PR-2B) DENV serotype 2 (DENV-2) clade, which emerged during the 1994 epidemic in Puerto Rico and replaced an endemic (PR-1) DENV-2 clade. The PR-2B DENV-2 produced increased levels of subgenomic flavivirus RNA (sfRNA) relative to genomic RNA during replication. PR-2B sfRNA showed sequence-dependent binding to and prevention of tripartite motif 25 (TRIM25) deubiquitylation, which is critical for sustained and amplified retinoic acid–inducible gene 1 (RIG-I)–induced type I interferon expression. Our findings demonstrate a distinctive viral RNA–host protein interaction to evade the innate immune response for increased epidemiological fitness.
Background: Nurses at the frontline of caring for COVID-19 patients might experience mental health challenges and supportive coping strategies are needed to reduce their stress and burnout. The aim of this study was to identify stressors and burnout among frontline nurses caring for COVID-19 patients in Wuhan and Shanghai and to explore perceived effective morale support strategies. Method: A cross-sectional survey was conducted in March 2020 among 110 nurses from Zhongshan Hospital, Shanghai, who were deployed at COVID-19 units in Wuhan and Shanghai. A COVID-19 questionnaire was adapted from the previous developed "psychological impacts of SARS" questionnaire and included stressors (31 items), coping strategies (17 items), and effective support measures (16 items). Burnout was measured with the Maslach Burnout Inventory. Results: Totally, 107 (97%) nurses responded. Participants mean age was 30.28 years and 90.7% were females. Homesickness was most frequently reported as a stressor (96.3%). Seven of the 17 items related to coping strategies were undertaken by all participants. Burnout was observed in the emotional exhaustion and depersonalization subscales, with 78.5 and 92.5% of participants presenting mild levels of burnout, respectively. However, 52 (48.6%) participants experienced a severe lack of personal accomplishment. Participants with longer working hours in COVID-19 quarantine units presented higher emotional exhaustion (OR = 2.72, 95% CI 0.02-5.42; p = 0.049) and depersonalization (OR = 1.14, 95% CI 0.10-2.19; p = 0.033). Participants with younger age experienced higher emotional exhaustion (OR = 2.96, 95% CI 0.11-5.82; p = 0.042) and less personal accomplishment (OR = 3.80, 95% CI 0.47-7.13; p = 0.033). Conclusions: Nurses in this study experienced considerable stress and the most frequently reported stressors were related to families. Nurses who were younger and those working longer shift-time tended to present higher burnout levels. Psychological support strategies need to be organized and implemented to improve mental health among nurses during the COVID-19 pandemic.
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