Scientists provide new insights into LASV GP-host interactions
Lassa virus (LASV) is the causative agent of Lassa fever, which is estimated to cause 100,000-300,000 infections annually in West Africa, with approximately 5,000 deaths. The glycoprotein (GP) of LASV mediates viral entry into host cells, and correct processing and modification of GP by host factors is a prerequisite for virus replication. However, little is known about the host factors on which the virus depends for this process.
In a recent study by the research group led by Prof. XIAO Gengfu in Wuhan Institute of Virology of the Chinese Academy of Sciences, a comprehensive LASV GP interactome was characterized, and further study revealed that STT3B-dependent N-glycosylation was preferentially required by arenavirus GPs and critical for virus infectivity.
In this study, an affinity purification coupled mass spectrometry (AP-MS) strategy was used to identify host proteins interacting with LASV GP, and the oligosaccharyltransferase (OST) complex was highlighted. The two specific thioredoxin subunits of STT3B-OST, magnesium transporter 1 (MAGT1) and tumor suppressor candidate 3 (TUSC3) were found to be essential for the N-glycosylation of viral GP. NGI-1, a small-molecule inhibitor of OST, also showed a robust inhibitory effect on arenavirus.
In conclusion, their study provides new insights into LASV GP-host interactions and extends the potential targets for the development of novel therapeutics against Lassa fever in the future.
The study was published in Journal of Virology entitled “Comprehensive Interactome Analysis Reveals that STT3B is Required for the N-Glycosylation of Lassa Virus Glycoprotein”.
This work was supported by the National Science and Technology Major Project, the National Key R&D Program of China, the National Natural Science Foundation of China, the Youth Innovation Promotion Association of the Chinese Academy of Sciences, and the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory of the Chinese Academy of Sciences.
The preferential requirement for STT3B-dependent N-glycosylation was conserved among arenavirus GPs. Image by XIAO Gengfu