Transgenic Expression of Human C-Type Lectin Protein CLEC18A Reduces Dengue Virus Type 2 Infectivity in Aedes aegypti

Frontiers in Immunology

Shie-Liang Hsieh³  Matthew P. Su⁴  Ya-Lang Huang⁶  Yun-Ting Tsou⁷  Chia-Hao Chien⁸  Jian-Chiuan Li⁹  Shih-Cheng Wu^1,10  Chun-Hong Chen^1,10  Wei-Liang Liu^1,10  Kun-Lin Liu^1,10  Jih-Jin Tsai^1,11  Lie Cheng^1,12 

[1] 0Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan;1Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan;2Institute for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan;Department of Biological Science, Nagoya University, Nagoya, Japan;Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;Genomics Research Center, Academia Sinica, Taipei, Taiwan;Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, Taiwan;Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan;National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan;National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli, Taiwan;School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;Tropical Medicine Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;

关键词: transgenic Aedes aegypti;    dengue virus (DENV);    CLEC18A;    innate immune pathways;    midgut microbiome;    mosquito;   

DOI  :  10.3389/fimmu.2021.640367

来源: DOAJ

【 摘 要 】

The C-type lectins, one family of lectins featuring carbohydrate binding domains which participate in a variety of bioprocesses in both humans and mosquitoes, including immune response, are known to target DENV. A human C-type lectin protein CLEC18A in particular shows extensive glycan binding abilities and correlates with type-I interferon expression, making CLEC18A a potential player in innate immune responses to DENV infection; this potential may provide additional regulatory point in improving mosquito immunity. Here, we established for the first time a transgenic Aedes aegypti line that expresses human CLEC18A. This expression enhanced the Toll immune pathway responses to DENV infection. Furthermore, viral genome and virus titers were reduced by 70% in the midgut of transgenic mosquitoes. We found significant changes in the composition of the midgut microbiome in CLEC18A expressing mosquitoes, which may result from the Toll pathway enhancement and contribute to DENV inhibition. Transgenic mosquito lines offer a compelling option for studying DENV pathogenesis, and our analyses indicate that modifying the mosquito immune system via expression of a human immune gene can significantly reduce DENV infection.

【 授权许可】

Unknown