Prior #influenza virus #infection alleviates an #arbovirus #encephalitis by reducing viral titer, #inflammation, and cellular infiltrates in the central nervous system

ABSTRACT

Respiratory and encephalitic virus infections represent a significant risk to public health globally. Detailed investigations of immunological responses and disease outcomes during sequential virus infections are rare. Here, we define the impact of influenza virus infection on a subsequent virus encephalitis. We used a model system in which mice were given influenza A virus (IAV) infection 8 days prior to Semliki Forest virus (SFV) infection (IAV→SFV). IAV infection clearly attenuated the subsequent SFV infection with reduced titers of infectious SFV and lower levels of cytokines and chemokines in the central nervous system (CNS). In contrast, the SFV viremia in both IAV→SFV and SFV-only mice was comparable. Increased type I interferon (IFN) levels in the CNS after IAV infection might have contributed to some level of protection towards SFV infection in the CNS, suggesting that early control of SFV replication in the CNS during IAV→SFV infection led to reduced adaptive response, given the lower number of CD8+ T cells recruited to the brain in IAV→SFV infection. In lungs, however, prior IAV infection elicited effector CD8+ T cells with highly activated CD38 and/or CD25 phenotypes, while SFV-only infection elicited distinct effector CD8+ T cells with increased frequencies of KLRG1 expression, a hallmark of short-lived effector T cells. Taken together, our findings demonstrate that prior IAV infection can confer protective immunity toward secondary SFV infection, confirmed by reduced disease severity and inflammatory immune responses in the brain. Our work provides important insights into therapies and vaccine regimens directed against unrelated pathogens.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.02108-24?af=R

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