Abstract
Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we have shown that RVA-16 3C protease cleaves Receptor-interacting protein kinase-1 (RIPK1), a key host factor that modulates various cell death and cell survival pathways. In the current study, we have investigated whether this cleavage is conserved across selected RV strains. RIPK1 was cleaved in cells infected with strains representing diversity across phylogenetic groups (A and B) and receptor usage (major and minor groups). The cleavage was abrogated in the presence of the specific 3C protease inhibitor, Rupintrivir. Interestingly, there appears to be involvement of another protease (maybe 2A protease) in RIPK1 cleavage in strains belonging to genotype B. Our data show that 3C protease from diverse RV strains cleaves RIPK1, highlighting the importance of the cleavage to the RV lifecycle.
Highlights
The efficiency of productive viral infection relies on the ability of a virus to establish infection within a single cell and viruses have evolved capabilities to control the cellular environment to escape the innate immune response, prolong host-cell survival, limit antigen-presentation, promote viral replication, and facilitate virus assembly or release.The execution of apoptosis may result in cleavage of factors required for viral genome replication, translation, autophagy, and virus release, and cell shutdown, preventing viral replication
In some samples, more than one cleavage product was detected with the anti-Receptor-interacting protein kinase-1 (RIPK1) antibody, with size differences observed between group A and B viruses
Densitometric samples, more than one cleavage product was detected with the anti-RIPK1 antibody, with size differences observed between group A and B viruses
Summary
The efficiency of productive viral infection relies on the ability of a virus to establish infection within a single cell and viruses have evolved capabilities to control the cellular environment to escape the innate immune response, prolong host-cell survival, limit antigen-presentation, promote viral replication, and facilitate virus assembly or release. The execution of apoptosis may result in cleavage of factors required for viral genome replication, translation, autophagy, and virus release, and cell shutdown, preventing viral replication. Programmed cell death (PCD) is a host response to virus infection in order to limit the spread of infection and contain the damage. The suppression of proapoptotic factors may be a viral strategy to shut down innate immune responses. Several Picornaviruses have evolved to control cell death signalling by multiple mechanisms, as reviewed in [2]
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