Researchers have shed light on the complex dynamics of bunyavirus transmission, identifying the non-structural protein NSm as pivotal to the virus’s ability to move between mosquito hosts and vertebrate populations.
The Bunyavirales order includes numerous viruses transmitted via blood-feeding arthropods like mosquitoes, which host and spread significant pathogens affecting human and animal health. Notably, the transmission of these viruses has been challenging to track, with questions existing around why only specific bunyaviruses have evolved to be effectively transmitted by arthropods.
A recent study conducted by researchers from various institutions, including the UK Medical Research Council, unveiled groundbreaking insights about the NSm protein, previously known for its unclear function across different bunyaviruses. Using Bunyamwera virus (BUNV) and the Aedes aegypti mosquito, the team demonstrated through cell culture studies and live mosquito tests its necessity for successful viral transmission.
According to the researchers, “NSm is required for cell-to-cell spread and egress from the mosquito midgut, which is a known barrier to viral infection.” Detailed experiments indicated this protein is dispensable for viral replication within mosquito cells but is absolutely necessary for effective infection following blood meals. Specifically, NSm is required for the virus to spread within the midgut, thwarting its ability to disseminate to other tissues.
During the study, mosquitoes fed on infected blood containing NSm-deficient BUNV demonstrated significantly reduced viral loads and failed to transmit the virus effectively. Upon comparison, mosquitoes infected with the wild-type virus exhibited substantial viral titres, highlighting the NSm protein's direct impact on infection rates.
The findings led the authors to conclude, “Our study reveals the evolutionary importance of the NSm protein as it allows bunyaviruses to transmit effectively between vertebrate and arthropod hosts.” This research not only illuminates the mechanism of viral spread but also raises concerns about the broader public health application.
Given the increasing incidence of arboviral diseases globally, with climate change amplifying risks, the results indicate the potential utility of attenuated vaccines against these viruses. Since NSm is not found in insect-specific bunyaviruses, the research highlighted opportunities for developing vaccines which target NSm-deficient strains, avoiding potential spillover during vector control.
The research team also discovered through experiments bypassing the midgut barrier, “Bypassing the midgut barrier showed no need for NSm for viral dissemination, highlighting its specific role within this compartment.” This pinpointed NSm as integral to transmission within the mosquito midgut but unnecessary for the general dissemination of the virus to parts like the salivary glands.
The evolutionary roots of NSm paint the protein as potentially acquiring its function via convergent evolution as different bunyaviruses adapted to similar environments. This remarkable discovery stands to not only advance scientific knowledge but also guide future studies on vector-borne viruses and their pathogenic mechanisms.
Overall, this work stresses the significance of NSm as more than just another viral component, portraying it as central to the propagation and public health risks posed by bunyaviruses transmitted via arthropod vectors.