Chang Ya-Chen, Liu Wei-Liang, Fang Pai-Hsiang, Li Jian-Chiuan, Liu Kun-Lin, Huang Jau-Ling, Chen Hsin-Wei, Kao Chih-Fei, Chen Chun-Hong
National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli 35053, Taiwan.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
PNAS Nexus. 2024 May 16;3(5):pgae188. doi: 10.1093/pnasnexus/pgae188. eCollection 2024 May.
C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and viral pathogenesis, little is known about their role in regulating dengue virus (DENV) infection and transmission. In this study, we established a homozygous knockout mutant line using CRISPR/Cas9 to study the interaction between and viruses in mosquito vectors. Furthermore, mouse experiments were conducted to confirm the transmission of DENV by mutants. We found that was mainly expressed in the medial lobe of the salivary glands (SGs) in female . knockout increased DENV replication and accumulation in the SGs of female , suggesting that plays an important role in DENV transmission. We also found a reduced expression of immunodeficiency and Janus kinase/signal transducer and activator of transcription pathway components correlated with increased DENV viral titer, infection rate, and transmission efficiency in the mutant strain. The findings of this study provide insights not only for guiding future investigations on the influence of CTLs on immune responses in mosquitoes but also for developing novel mutants that can be used as vector control tools.
C型凝集素(CTLs)是一类碳水化合物结合蛋白,是蚊虫唾液的重要组成部分。尽管CTLs在免疫激活和病毒发病机制中起关键作用,但关于它们在调节登革病毒(DENV)感染和传播中的作用却知之甚少。在本研究中,我们利用CRISPR/Cas9建立了一个纯合敲除突变株系,以研究蚊虫载体中[具体物质]与病毒之间的相互作用。此外,还进行了小鼠实验以证实[具体物质]突变体对DENV的传播作用。我们发现[具体物质]主要在雌性[蚊虫种类]唾液腺(SGs)的中叶表达。[具体物质]敲除增加了雌性[蚊虫种类]唾液腺中DENV的复制和积累,表明[具体物质]在DENV传播中起重要作用。我们还发现,在[具体物质]突变株中,免疫缺陷以及Janus激酶/信号转导和转录激活因子通路成分的表达降低,这与DENV病毒滴度、感染率和传播效率的增加相关。本研究结果不仅为指导未来关于CTLs对蚊虫免疫反应影响的研究提供了见解,也为开发可作为病媒控制工具的新型突变体提供了思路。