登革热，寨卡病毒和其他蚊子在蚊子中传播的其他黄病毒艾德斯属是一个主要公共卫生问题，每年使数亿人生病并杀死成千上万的人。这些arbovirus有望更好地传输，并且to more people geographically将来在我们温暖的气候中。几千年来，人们已经认识到，在蚊子传播的疾病暴发期间，这些疾病的患者需要在康复期间保护这些疾病的患者免受进一步的蚊子叮咬（例如用床网），以限制这些疾病对健康人的传播。部分原因是，由于症状的症状，康复的患者可能不太能够保护自己免受蚊子的叮咬，部分原因是蚊子可能更吸引因蚊子传播疾病而厌倦的人。这种策略在进化上对蚊子传播的病原体有利，以最大化其传播。有证据表明，通过操纵宿主，人们对蚊子传播的疾病感染了人们对寻求鲜血的女性蚊子的吸引力。例如，我们知道Plasmodium parasites产生一种类异on-前体，增加人类红细胞挥发性混合物的释放，这使得感染疟疾的小鼠对蚊子媒介的吸引力显着吸引人。但是，到目前为止，我们不知道Arbovirus是否通过艾德斯蚊子会类似地操纵其宿主以最大程度地传播疾病。
在一场旅行中study，洪张，Yibin Zhu及其同事在Tsinghua University表明，Flavivivirus感染的小鼠对寻求血液的吸引力明显更具吸引力艾德斯蚊子。允许蚊子选择在三笼和两笼嗅觉仪中移动到更接近健康或感染小鼠的笼子。蚊子的偏好与宿主发出的挥发物有关，这显示出偏好被挥发性清除消除。
Analyzing how the antennae of female mosquitoes reacted to the volatiles of healthy and infected mice, the researchers found that mosquitoes responded significantly to acetophenone, decanal and styrene, but not to other volatiles. Acetophenone attracted more mosquitoes when put on healthy mice, or on a human hand, compared with just the solvent. Using GC-MS, ten-to-hundred times as much acetophenone was found to be released by Zika-virus and dengue-infected compared to healthy mice.
Volatiles taken from the armpits of dengue patients attracted significantly more mosquitoes than just the solvent, or volatiles taken from the armpits of healthy donors. The volatiles taken from the armpits of dengue patients also contained ten-to-hundred times as much acetophenone compared to the volatiles taken from armpits of healthy donors.
当去除感染了寨卡病毒或登革热病毒的小鼠的皮肤细菌时，消除了蚊子对感染小鼠的偏爱，但没有去除肠道细菌，表明乙烯酮释放与小鼠的皮肤细菌有关。当去除黄病毒感染的小鼠的皮肤细菌时，乙醇酮的释放也降低到与健康小鼠相似的水平，而当去除其肠道细菌时不会。
登革热和ZIKV感染的小鼠的细菌具有十倍，与健康小鼠相比，芽孢杆菌和葡萄球菌相对丰度增加，但乳酸杆菌的相对丰度降低。当在无菌小鼠的皮肤上培养时，细菌会产生大量的乙二酮，并在足够浓度的情况下引起了嗅觉仪中寻求鲜血的雌性蚊子的吸引。
Resistin-like molecula-α, an antimicrobial protein specifically expressed by epidermal keratinocytes and sebocytes was expressed at significantly reduced levels in the skin of Zika-virus and dengue-infected mice, compared to healthy controls, based on RNA-seq, qPCR and Western blot. This protein, as well as it’s human analog, RETN, significantly reduced the viability of the acetophenone-producing Bacillus bacteria, compared to other bacteria. Based on previous research, RELM-α can be induced by dietary vitamin A derivatives, such as isotretinoin.
Relm-Alpha的产生在寨卡病毒和登革热感染的小鼠中恢复到健康水平，这些小鼠通过口服口服给药，这些小鼠皮肤上的细菌细菌的相对丰度也与健康小鼠也没有显着差异。此外，尽管寨卡病毒和登革热感染，但雌性寻求鲜血的蚊子并未优先吸引被异托摩酸的小鼠。大约一半的蚊子被送入登革热病毒和寨卡病毒感染的小鼠时被感染的蚊子被感染，而蚊子被感染的小鼠被送入异丙肾上腺素蛋白，而其Zika病毒滴度没有显着差异。
总而言之，作者发现寨卡病毒和登革热病毒抑制了Relm-Alpha的产生，从而允许细菌的扩散，从而增加了乙醇酮的产生，这是吸引人们寻求蚊子的有效吸引。此外，同维诺二氨基蛋白的给药可以阻碍此过程，增加了α-α，减少细菌和乙醇酮的产生。
One of the strengths of this study is that it provides a thorough analysis of this important subject, and it combines a large number of studies employing a variety of techniques from mosquito choice assays to electroantennograms to GS-MS to RNA-seq to microbiological studies in the quest to find the mechanism by which mosquitoes prefer infected mice and people. The study provides strong evidence that flaviviruses modify their host’s microbiome to increase the production of volatiles that attract mosquito vectors, ensuring their transmission to other hosts. This is similar to how Plasmodium parasites increase the release of volatile blends by human red blood cells to attract more Anopheles mosquitoes. There are also similar examples from insect-transmitted plant pathogens, such as where the黄瓜镶嵌病毒makes infected squash plants produce a volatile blend that attracts aphids despite the low quality of the infected plant. These results suggest that we have a whole another reason to protect people infected with flaviviruses from mosquito bites, because even with all else equal, they will attract more mosquitoes.
这项研究的另一个令人兴奋的部分是证明了饮食中的维生素是衍生物，异维诺蛋白，能够扭转感染动物的吸引力，只有大约一半的蚊子以宿主感染。这尤其令人兴奋，因为它表明，除了保护疗养者免受带有屏幕和床头的蚊子免受蚊子的侵害外，我们还可以使用低成本，易于施用，安全的药物来抵抗它们对蚊子的吸引力。异维使用素已经用于以品牌名称治疗痤疮Accutane，所以可能只是重新利用对于这种新迹象，与全新药物相比，这将容易得多，更快地许可。但是，我们需要记住，这项研究主要是在小鼠上进行的，除了从人的腋下挥发物和测试化合物手中的挥发物。下一步可能是对登革热或寨卡患者进行双盲随机研究，以查看服用异托诺蛋白是否会增加皮肤中的RETN产生，减少芽孢杆菌相对丰度和乙醇酮的产生，并最终对女性血液的吸引力寻找蚊子。如果结果在人类研究中仍然可比，我们可以减少从感染者那里吸收寨卡病毒或登革热病毒的蚊子的数量，从而大大导致控制这些黄病毒。
最后，在当前研究中负责提高感染小鼠的吸引力的挥发性，乙烯酮, is widely used in fragrances and perfumes, due to its floral, sweet scent to people. Thus, next time you go to areas that are endemic for dengue, Zika, or other flaviviruses, or just have large艾德斯populations (such as Eastern North America), which will increase in the future, make sure to check that the香味您穿的不包括乙烯酮！
评论