Restriction of Zika virus infection and transmission in Aedes aegypti mediated by an insect-specific flavivirus

Restriction of Zika virus infection and transmission in Aedes aegypti mediated by an insect-specific flavivirus
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DOI:
10.1038/s41426-018-0180-4
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发表时间:
2018-11-15
影响因子:
13.2
通讯作者:
Brault, Aaron C.
Brault, Aaron C.
中科院分区:
医学2区
文献类型:
--
作者:
Romo, Hannah;Kenney, Joan L.;Brault, Aaron C.

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Nhumirim病毒(Nhumirim virus,NHUV)是一种昆虫特异性黄病毒,能抑制西尼罗病毒(West Nile virus,WNV)在致倦库蚊(Culex quinquefasciatus)体内的生长,降低其传播率。为了评估NHUV是否可能干扰其他医学上重要的黄病毒的传播,在白纹伊蚊细胞中评估了NHUV抑制寨卡病毒(ZIKV)和登革热-2病毒(DENV-2)的病毒生长的能力。在同时接种NHUV或预接种NHUV的细胞中观察到ZIKV(100,000倍)和DENV-2(10,000倍)显着减少。相比之下,甲病毒基孔肯雅病毒仅观察到短暂的10倍滴度降低。此外,ZIKV的体外蚊子生长受限与NHUV共接种培养物中细胞内ZIKV RNA水平降低相关。为了评估NHUV是否可以调节ZIKV的载体感受态,将NHUV接种的埃及伊蚊口服暴露于ZIKV。与未暴露于NHUV的蚊子(51%)相比,接种NHUV的蚊子表现出显著更低的ZIKV感染率(18%)(p < 0.002)。类似地,与仅ZIKV接种的蚊子(78%)相比,对于NHUV/ZIKV双重胸内接种的蚊子(41%)观察到较低的ZIKV传播率(p < 0.0001),表明NHUV可以干扰Ae中ZIKV的中肠感染和唾液腺感染。埃及人。这些结果表明,NHUV可用于模拟重复感染排除机制,并研究蚊子病毒组影响医学上重要的黄病毒传播的潜力。
Previous studies demonstrated an insect-specific flavivirus, Nhumirim virus (NHUV), can suppress growth of West Nile virus (WNV) and decrease transmission rates in NHUV/WNV co-inoculated Culex quinquefasciatus. To assess whether NHUV might interfere with transmission of other medically important flaviviruses, the ability of NHUV to suppress viral growth of Zika virus (ZIKV) and dengue-2 virus (DENV-2) was assessed in Aedes albopictus cells. Significant reductions in ZIKV (100,000-fold) and DENV-2 (10,000-fold) were observed in either cells concurrently inoculated with NHUV or pre-inoculated with NHUV. In contrast, only a transient 10-fold titer reduction was observed with an alphavirus, chikungunya virus. Additionally, restricted in vitro mosquito growth of ZIKV was associated with lowered levels of intracellular ZIKV RNA in NHUV co-inoculated cultures. To assess whether NHUV could modulate vector competence for ZIKV, NHUV-inoculated Aedes aegypti were orally exposed to ZIKV. NHUV-inoculated mosquitoes demonstrated significantly lower ZIKV infection rates (18%) compared to NHUV unexposed mosquitoes (51%) (p < 0.002). Similarly, lower ZIKV transmission rates were observed for NHUV/ZIKV dually intrathoracically inoculated mosquitoes (41%) compared to ZIKV only inoculated mosquitoes (78%) (p < 0.0001), suggesting that NHUV can interfere with both midgut infection and salivary gland infection of ZIKV in Ae. aegypti. These results indicate NHUV could be utilized to model superinfection exclusion mechanism(s) and to study the potential for the mosquito virome to impact transmission of medically important flaviviruses.