Human telomerase reverse transcriptase supports respiratory syncytial virus replication

Respiratory syncytial virus (RSV), discovered in 1956 and identified in children in 1957, is the major respiratory pathogen of infants and children under the age of 5 worldwide. RSV remains a significant challenge, despite recent advancements of vaccine development and monoclonal antibody prophylaxis. While specific antiviral agents have shown success as therapeutics for many other viruses, viral mutations inevitably develop, making these therapeutic interventions ineffective due to viral resistance. This unavoidable obstacle warrants alternative approaches to targeting host cellular factors that are essential for viral replication regardless of viral mutations. Our goal was to assess the feasibility of this approach. In doing so, we sought to determine the cellular enzymes and functions that are required for RSV replication. Here, we demonstrate that inhibiting human telomerase reduced or abolished viral protein production. Further, we showed that RNA helicase eIF4A is essential for RSV protein and progeny production. Lastly, targeting nuclear transport receptor reduces RSV RNAs and proteins synthesis, suggesting a role of host nucleus for viral replication. Overall, the inhibition of virus replication-dependent host functions may be an effective means to combat viral infections and would sidestep the inevitable resistance that emerges with virus-specific strategies.