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伊蚊共生细菌对蚊媒黄病毒传播的影响

Influence of Symbiotic Bacteria of Aedes Mosquito on the Transmission of Mosquito-borne Flaviviruses

作者:张礼铭
  • 学号
    2019******
  • 学位
    博士
  • 电子邮箱
    zlm******.cn
  • 答辩日期
    2024.05.20
  • 导师
    程功
  • 学科名
    生物学
  • 页码
    131
  • 保密级别
    公开
  • 培养单位
    501 基础医学院
  • 中文关键词
    登革病毒;寨卡病毒;伊蚊;罗森伯格式菌;葡萄糖脱氢酶
  • 英文关键词
    Dengue virus; Zika virus; Aedes mosquito; Rosenbergiella; Glucose dehydrogenase

摘要

蚊媒黄病毒是导致严重人类疾病的病原体,包括登革病毒和寨卡病毒。这些黄病毒每年导致数亿人感染和许多人死亡。蚊媒黄病毒在脊椎动物宿主和蚊虫媒介之间维持其生命周期,蚊虫通过吸食血液从病毒宿主获得感染性颗粒。这些颗粒进入肠道上皮细胞,随后感染血淋巴等组织,并迁移到唾液腺,从而使受感染的蚊虫在下一次叮咬中传播病毒。因此,蚊虫肠道是病毒感染的关键部位。 蚊虫的肠道中蕴藏着丰富的微生物群落。这些共生菌群不仅与蚊虫保持着体内平衡,还在决定病毒传播能力方面发挥着复杂的作用。因此,肠道菌群被认定为蚊媒病毒感染和传播的关键因素。白纹伊蚊是我国云南省登革热流行的主要媒介,本研究从野外白纹伊蚊肠道中分离出了55种可培养细菌。其中,罗森伯格式菌YN46(Rosenbergiella sp. YN46,Rosenbergiella_YN46)菌株显著提高了白纹伊蚊和埃及伊蚊对登革病毒和寨卡病毒的抵抗力。此外,Rosenbergiella_YN46能够长期定植于伊蚊的肠道中,通过分泌葡萄糖脱氢酶(RyGDH)抑制黄病毒感染肠道上皮。在蚊虫吸血时,RyGDH将葡萄糖转化为葡萄糖酸,迅速降低肠道pH至约6.0,导致黄病毒失活,从而防止病毒侵入肠道上皮细胞。 环境在塑造成蚊的微生物群落结构中起着核心作用。肠道细菌除了可以通过蚊虫母代遗传给子代外,也可以通过幼虫和成虫的摄食过程而不断演变和丰富。因此,来自不同栖息地的蚊虫可能拥有独特的肠道菌群,并且这种差异进一步影响了蚊虫的媒介能力。本研究发现,云南省不同地点白纹伊蚊种群的Rosenbergiella_YN46携带率存在显著差异。在登革热病例较少的文山和普洱地区,蚊虫携带Rosenbergiella_YN46的比例较高,而在登革热流行的西双版纳和临沧地区,蚊虫携带该菌的比例较低。在半现场试验中,蚊虫孳生地中的Rosenbergiella_YN46能够传播到成年西双版纳白纹伊蚊种群中,这表明它具有跨龄传递的能力,从而有可能阻止成年伊蚊传播登革病毒。 本研究强调了基于Rosenbergiella_YN46的干预策略在预防黄病毒疾病方面的潜力,为未来的疾病控制策略提供了新的思路。

Flavivirus is a pathogen, including dengue virus and Zika virus, that causes severe human diseases. These viruses infect billions of people annually, resulting in numerous deaths. The mosquito-borne flavivirus maintains its lifecycle between vertebrate hosts and mosquito vectors, with mosquitoes becoming infected by feeding on the blood of virus hosts. The infectious particles enter the gut epithelial cells, subsequently infecting hemolymph and other tissues, and then migrate to the salivary glands, allowing the infected mosquito to transmit the virus during the next bite. Therefore, the mosquito gut is a critical site for virus infection. The mosquito gut harbors a diverse microbial community. These symbiotic bacterial communities not only help maintain the internal balance of mosquitoes but also play a complex role in determining the virus transmission ability. Consequently, the gut microbiota is recognized as a key factor in vector-borne virus infection and transmission. In this study, 55 cultivable bacterial species were isolated from the field-caught Aedes albopictus mosquitoes‘ gut. Among them, the Rosenbergiella sp. YN46 significantly enhanced the resistance of A. albopictus and Aedes aegypti mosquitoes to dengue virus and Zika virus. Furthermore, Rosenbergiella_YN46 could persistently colonize the mosquito gut, inhibiting flavivirus infection in gut epithelial cells by secreting glucose dehydrogenase (RyGDH). During blood feeding, RyGDH converts glucose to gluconic acid, rapidly lowering the gut pH to approximately 6.0, inactivating the flavivirus and preventing its invasion of gut epithelial cells. The environment plays a central role in shaping the microbial community structure of mosquito guts. Although certain gut bacteria may be passed on to offspring through maternal inheritance, the gut microbial community also evolves and enriches during the larval and adult mosquito feeding processes. Therefore, mosquitoes from different habitats may have unique gut bacterial communities, and this difference further influences the mosquitoes‘ vectoring abilities. This study found significant differences in the prevalence of Rosenbergiella_YN46 in A. albopictus populations from different locations in Yunnan province, China. In areas with fewer dengue fever cases, such as Wenshan and Puer, mosquitoes had a higher prevalence of Rosenbergiella_YN46, while in areas with a dengue fever epidemic, such as Xishuangbanna and Lincang, the prevalence of this bacterium was lower. In a semi-field experiment, Rosenbergiella_YN46 from mosquito breeding sites could spread to the adult Xishuangbanna A. albopictus population, indicating its ability for transstadial transmission, which could potentially prevent adult mosquitoes from transmitting dengue fever virus. This study emphasizes the potential of interventions based on Rosenbergiella_YN46 in preventing flavivirus diseases, providing new insights for future disease control strategies.