Reduced Nucleoprotein Availability Impairs Negative-Sense RNA Virus Replication and Promotes Host Recognition

Negative-sense RNA viruses (NSVs) utilize RNA-dependent RNA polymerases (RdRp) and nucleoproteins (NPs) to replicate their genome and transcribe mRNAs. These components form viral ribonucleoprotein complexes that play a crucial role in maintaining viral genetic material. A study investigated the impact of reduced NP levels in influenza A virus and Sendai virus through the manipulation of host microRNA expression. The results revealed that decreased NP levels not only led to a significant reduction in genome replication, but also triggered a heightened host antiviral response. Insufficient NP hindered the replication machinery of NSVs from processing full-length genomes, generating abnormal replication products that triggered host immune responses. This response was facilitated by the recognition by pathogen-associated molecular patterns, resulting in a robust host antiviral defense. Interestingly, the effects of limiting NP levels were consistent across various NSVs, including Ebola virus, Lassa virus, and measles virus. This study sheds light on the delicate balance that NSVs must strike between efficient replication and avoiding host immune responses. The findings offer insights into viral genome replication mechanisms and suggest potential avenues for developing effective antiviral strategies, adjuvants, and live-attenuated vaccines. 

(LA)