# Bovine respiratory syncytial virus utilizes the human insulin-like growth factor 1 receptor in the late stages of infection

## TL;DR

This study shows that the bovine respiratory syncytial virus uses the human insulin-like growth factor 1 receptor to spread efficiently in later stages of infection.

## Contribution

The study reveals a novel role of IGF1R in the late stages of BRSV infection, not required for initial entry.

## Key findings

- A recombinant BRSV with a ZsGreen reporter gene was successfully generated and showed similar growth to the wild-type virus.
- HEK293T cells were found to be permissive to BRSV infection.
- IGF1R is not essential for early BRSV infection but supports efficient viral propagation at later stages.

## Abstract

Bovine respiratory syncytial virus (BRSV) is a major viral pathogen associated with the bovine respiratory disease complex, which is a leading cause of morbidity, mortality and economic loss in the cattle industry worldwide. Clinical infection is most severe in young calves, where it commonly causes lower respiratory tract inflammation, bronchopneumonia and predisposition to secondary bacterial infections. In experimental research, BRSV is typically maintained in Vero and MDBK cells. Although reverse genetics systems have been established for BRSV, we developed a bacterial artificial chromosome-based reverse genetics system for the virus. We successfully recovered a recombinant BRSV with the ZsGreen reporter gene inserted between the P and M genes. The recombinant virus displayed comparable growth kinetics to the WT strain, demonstrating the utility of the system for generating reporter viruses. Reporter virus infectivity assessments in mammalian MDBK, VeroE6, HEp-2 and HEK293T cells revealed that HEK293T cells are permissive to BRSV. To investigate the potential role of human insulin-like growth factor 1 receptor (hIGF1R), which human RSV uses for entry, we infected insulin-like growth factor 1 receptor (IGF1R)-knockout (KO) 293 T cells with BRSV-ZsGreen. At 24 h post-infection (hpi), ZsGreen levels were similar between WT and hIGF1R-KO cells; however, by 72 hpi, viral spread was markedly reduced in hIGF1R-KO cells and correlated with IGF1R levels. These findings suggest that IGF1R is dispensable for early BRSV infection but contributes to efficient viral propagation in later stages.