IFNβ deficiency in mice infected with Sindbis virus led to earlier and more severe symptomatic disease, increased early viral replication, and altered monocyte and NK cell recruitment.
IFNβ plays a critical role in modulating the early innate immune response and restricting viral replication to delay disease onset in alphavirus encephalomyelitis.
Alphaviruses are mosquito-borne viruses that can infect the central nervous system (CNS) and cause encephalomyelitis, which is a rare but dangerous complication from infection. In mice, this can be studied in a model of infection with Sindbis virus (SINV), which infects neurons and causes neurological disease. Due to the non-renewable nature of neurons, the immune response in the CNS is specialized to prevent neuronal damage or death, even if they are infected. Therefore, insights into the nuances of antiviral immunity in the CNS provide a better understanding of disease pathogenesis and mechanisms of recovery. Type I interferons (IFNs) are critically important for survival; they are an innate antiviral defense mechanism that consists mainly of IFNα and IFNβ. Although both use the same receptor, type-specific differences between IFNα and IFNβ have been described in other contexts. To this end, Ifnb−/− mice were used to elucidate the role of IFNβ in recovery from alphavirus encephalomyelitis. IFNβ-deficient mice have intact IFNα expression and downstream signaling, but symptomatic disease occurs earlier and is more severe. This is accompanied by increased virus replication in the early stages of infection. Microgliosis is reduced in Ifnb−/− mice compared to wildtype, but inflammatory cytokine/chemokine levels are higher and associated with alterations in monocyte and NK cell recruitment into the CNS. Ifnb−/− mice have no deficiencies in the expression of factors known to be required for viral clearance. Therefore, IFNβ modulates the early stages of the immune response and facilitates restriction of virus replication, contributing to delayed disease onset.
Nguyen et al. (Sat,) conducted a other in Alphavirus encephalomyelitis. IFNβ deficiency (Ifnb-/- mice) vs. Wildtype mice was evaluated on Disease severity and viral replication kinetics. IFNβ deficiency in mice infected with Sindbis virus led to earlier and more severe symptomatic disease, increased early viral replication, and altered monocyte and NK cell recruitment.