SARS-CoV-2 Mediated Inhibition Of Respiratory Syncytial Virus

Abstract

With circulation of SARS-CoV-2, fears about coinfection with other respiratory viruses such as influenza and RSV were significant, but the opposite was observed. Distancing/barriers played a major role in reducing other viral co-infections, however, some infrequent co-infections still occurred. We investigated the relationship between SARS-CoV-2 and RSV during coinfection to understand how they might compete or synergize. We found only RSVs replication was significantly reduced when coinfected with SARS-CoV-2. Investigation of the mechanism revealed that the SARS-CoV-2 protein Nsp1 disrupts the RSV M2-2 protein but not the upstream M2-1 protein on the same biscistronic mRNA transcript. The impact of Nsp1 on M2-2 was not dependent on M2-2 being the second ORF in a bicistronic mRNA transcript, but likely from prevention of ribosomal termination-reinitiation necessary for M2-2 production. Additional viral ORFs from influenza A, influenza B, or Sendai virus dependent on the same or other ribosomal initiation mechanisms were tested and we found only influenza B M/M2 which likely uses a similar method as M2-2 was disrupted. Various M2-2 constructs, with/without the proposed site of ribosomal termination-reinitiating, co-transfected with Nsp1 and were in agreement that disruption to M2-2 expression occurs if the site of re-initiation was present upstream. These data not only suggest Sars-CoV-2 can outcompete RSV through suppression of M2, but may also point to potential ways to interfere with RSV by targeted therapies.