A human-blood-derived microRNA facilitates flavivirus infection in fed mosquitoes
Yibin Zhu,
Chi Zhang,
Liming Zhang,
Yun Yang,
Xi Yu,
Jinglin Wang,
Qiyong Liu,
Penghua Wang,
Gong Cheng
Affiliations
Yibin Zhu
Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518000, China; Institute of Pathogenic Organisms, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, China
Chi Zhang
Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
Liming Zhang
Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
Yun Yang
Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
Xi Yu
Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
Jinglin Wang
Yunnan Tropical and Subtropical Animal Viral Disease Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming 650224, China
Qiyong Liu
State Key Laboratory of Infectious Disease Prevention and Control, Beijing 102206, China
Penghua Wang
Department of Immunology, School of Medicine, the University of Connecticut Health Center, Farmington, CT 06030, USA
Gong Cheng
Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518000, China; Institute of Pathogenic Organisms, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, China; Corresponding author
Summary: Hematophagous arthropods, such as mosquitoes, naturally carry and transmit hundreds of arboviruses to humans. Blood meal is a predominant physical interface that shapes cross-species communications among humans, bloodsuckers, and arboviruses. Here, we identify a human-blood-derived microRNA, hsa-miR-150-5p, that interferes with a mosquito antiviral system to facilitate flavivirus infection and transmission. hsa-miR-150-5p is acquired with a blood meal into the mosquito hemocoel and persists for a prolonged time there. The agomir of hsa-miR-150-5p enhances, whereas the antagomir represses flaviviral infection in mosquitoes and transmission from mice to mosquitoes. Mechanistic studies indicate that hsa-miR-150-5p hijacks the mosquito Argonaute-1-mediated RNA interference system to suppress the expression of some chymotrypsins with potent virucidal activity. Mosquito chymotrypsins are essential for resisting systemic flavivirus infection in hemocoel tissues. Chymotrypsin homologs potentially targeted by miR-150-5p are also found in other hematophagous arthropods, demonstrating a conserved miR-150-5p-mediated cross-species RNAi mechanism that might determine flaviviral transmissibility in nature.
