Potential effects of genetic variations in fusion protein on the virulence of human respiratory syncytial virus.

INTRODUCTION

The fusion glycoprotein (F protein) of human respiratory syncytial virus (HRSV) critically determines viral infectivity and host immune recognition. This study evaluated the effects of F protein genetic variations from the globally dominant HRSV genotypes ON1 and BA9 on viral replication dynamics and pathogenicity.

METHODS

Using a reverse genetics system, two recombinant HRSV strains, rLong-BJ1903-AF and rLong-SY2103-BF, were generated by replacing the F gene in the isogenic Long-bacterial artificial chromosome (BAC) backbone with F genes derived from the clinical isolates BJ19-03 (ON1 genotype) and SY21-03 (BA9 genotype), respectively. Their phenotypes were assessed in cellular and animal models.

RESULTS

In vitro, both recombinant viruses showed attenuated replication kinetics compared with the parental Long-BAC strain, with peak viral titers delayed by at least 12 h post-infection. In vivo, both recombinant viruses caused less severe disease than Long-BAC. Among them, rLong-SY2103-BF displayed greater pathogenicity than rLong-BJ1903-AF, as shown by slower body weight recovery, higher lung viral loads, elevated proinflammatory cytokine levels, and marked pulmonary pathological alterations.

DISCUSSION: These findings indicate that both recombinant viruses exhibit reduced replication capacity and less severe pathogenic phenotypes compared with the Long-BAC parental strain in this F-gene replacement system, providing a foundation for antiviral and immunological strategies targeting HRSV.