Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
Kunming Children's Hospital, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Institute of Pediatrics, Kunming, China.
J Med Virol. 2022 Sep;94(9):4338-4347. doi: 10.1002/jmv.27826. Epub 2022 May 14.
Dengue virus (DV) has occasionally emerged at epidemic levels in Yunnan, China. Vaccine development is limited by antibody-dependent enhancement and a lack of good animal models. Thus, the study investigated cross infection based on maternal immunity in BALB/c mice and assessed the risk of cross infection by DV2-D13113 and DV3-YNWS2 epidemic virus strains. DV replicated within the organs of the BALB/c infant mice, even causing death. Particularly, DV3-infected infant mice were at higher risk of severe disease if their mothers were infected with DV2. Although BALB/c adults and pups survived DV2/DV3 infection and produced anti-DV antibodies after 5-8 days, extensive subcutaneous vascular leakage was observed after secondary DV infection. Furthermore, vascular permeability in the lung and kidney significantly increased in offspring born to heterotypic virus-infected mothers. Thus, vascular leakage indicates severe DV infection. The results indicate that maternal immunity increases the severity of subsequent heterotypic infection. Additionally, secondary cross infection by D13113 and YNWS2 represents a risk of serious disease. This study has implications for studies of DV cross infection and vaccine development.
登革病毒（DV）偶尔在中国云南出现流行水平。疫苗的开发受到抗体依赖性增强和缺乏良好的动物模型的限制。因此，本研究基于母源免疫在 BALB/c 小鼠中进行了交叉感染研究，并评估了 DV2-D13113 和 DV3-YNWS2 流行病毒株的交叉感染风险。DV 在 BALB/c 婴儿小鼠的器官内复制，甚至导致死亡。特别是，如果母亲感染了 DV2，感染 DV3 的婴儿小鼠患重病的风险更高。尽管 BALB/c 成年小鼠和幼鼠在感染 DV2/DV3 后 5-8 天内存活下来并产生了抗 DV 抗体，但在二次 DV 感染后观察到广泛的皮下血管渗漏。此外，来自异源病毒感染母亲的后代的肺和肾脏中的血管通透性显著增加。因此，血管通透性表明严重的 DV 感染。结果表明，母源免疫增加了随后异源感染的严重程度。此外，D13113 和 YNWS2 的二次交叉感染代表了严重疾病的风险。本研究对登革病毒的交叉感染和疫苗开发研究具有重要意义。
