Identified in the 1940s in Africa, Zika is primarily spread by the bite of an infected mosquito. It can be passed from a pregnant woman to her fetus, leading to defects in infants, including microcephaly that causes abnormally small brains and heads. Since 2015, the Zika virus (ZIKV) has swept through more than 60 countries. The epidemic led the World Health Organization to issue an alert in December 2015. However, there is currently no vaccine or treatment for Zika.

Prof. LAI Ren from Kunming Institute of Zoology, Chinese Academy of Sciences (CAS), and his colleagues found a protein from the salivary glands ofAedes aegypti(yellow fever mosquito), named LTRIN, facilitated the transmission of the ZIKV.LTRIN was upregulated in blood-fed mosquitoes, and it facilitated ZIKV transmission and exacerbated ZIKV pathogenicity by interfering with signaling through the lymphotoxin-breceptor (LTbR), a member of the tumor necrosis factor receptor superfamily that protects against virus infection by regulating host immunity.

Mechanically, LTRIN bound to LTbR and preferentially inhibited NF-kB signaling and inflammatory cytokines production through interfering with LTbR dimerization during ZIKV infection. Furthermore, anti-LTRIN treatment inhibited mosquito-mediated ZIKV infection, and LTbR abrogation was demonstrated to potentiate ZIKV infectivity both in vitro and in vivo.

This is the first evidence showing that a specific mosquito salivary protein can exacerbate ZIKV pathogenesis in mammalian hosts and that LTbR signaling plays a critical role in ZIKV infection. This study sheds light on the process of ZIKV transmission in nature, which will improve our understanding of the causes of ZIKV outbreak and infectivity.

The findings also highlight the possible therapeutic potential of modulating LTRIN activity or vaccination of LTRIN to increase host defense against ZIKV infection and to develop effective treatment options for patients with debilitating mosquito-borne diseases.

JIN Lin, GUO Xiaomin, SHEN chuanbin, HAO Xue (Kunming Institute of Zoology, CAS) and SUN Peng (Tsinghua University) are the co-first authors of this paper. CHENG Gong (Tsinghua University), QI Xiaopeng and LAI Ren (Kunming Institute of Zoology, CAS) are the corresponding authors.  

This work was supported by fundings from the National Key Research and Development Program of China, National Natural Science Foundation of China, CAS and Yunnan Province. 

Model of mosquito salivary protein LTRIN exhibited augmentation for ZIKV infectivity (Image by LAI’s group)

By JIN Lin, Editor: HE Linxi

Contact:

HE Linxi

helinxi@mail.kiz.ac.cn