Host IP₃R channels are dispensable for rotavirus Ca²⁺ signaling but critical for intercellular Ca²⁺ waves that prime uninfected cells for rapid virus spread.

ABSTRACT:

Importance

Many viruses exploit host Ca²⁺ signaling to facilitate their replication; however, little is known about how Ca²⁺ signals from different host and viral channels contribute to the overall dysregulation of Ca²⁺ signaling or promote virus replication. Using cells lacking IP₃R, a host ER Ca²⁺ channel, we delineated intracellular Ca²⁺ signals within virus-infected cells and intercellular Ca²⁺ waves (ICWs), which increased Ca²⁺ signaling in neighboring, uninfected cells. In infected cells, IP₃R was dispensable for rotavirus-induced Ca²⁺ signaling and replication, suggesting the rotavirus NSP4 viroporin supplies these signals. However, IP₃R-mediated ICWs increase rotavirus replication kinetics and spread, indicating that the Ca²⁺ signals from the ICWs may prime nearby uninfected cells to better support virus replication upon eventual infection. This "pre-emptive priming" of uninfected cells by exploiting host intercellular pathways in the vicinity of virus-infected cells represents a novel mechanism for viral reprogramming of the host to gain a replication advantage.

SUBMITTER: Perry JL 

PROVIDER: S-EPMC10790754 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature