Respiratory syncytial virus nonstructural proteins 1 and 2 are crucial pathogenic factors that modulate interferon signaling and Treg cell distribution in mice

Respiratory syncytial virus (RSV) nonstructural (NS) proteins 1 and 2 have multiple functions in suppressing the innate immune response and modulating T helper cell subset differentiation. However, little is known about the roles of NS proteins as independent virulence factors. We investigated the effects of recombinant NS1- and NS2-expressing plasmids on the pathogenesis of murine respiratory tissues and splenetic Foxp3+ regulatory T (Treg) cell distribution. Both NS proteins caused weight loss in mice, and NS2 transfection resulted in a persistent weight loss. NS1 dramatically suppressed the induction of interferon beta and interferon-induced GTP-binding protein Mx1. NS1 and NS2 demonstrated different effects in regulating Treg cell differentiation; NS2 increased the proportion of Tregs, whereas NS1 suppressed it. Inhibiting either NS1 or NS2 alleviated the pathology of lung tissues. Thus, NS1 and NS2 are independent pathogenic factors and could be targets for therapeutic strategies in treating RSV infection.