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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Respiratory Virus-Specific and #Time-Dependent #Interference of #Adenovirus Type 2, #SARS-CoV-2 and #Influenza Virus #H1N1pdm09 During Viral Dual Co-Infection and Superinfection In Vitro

Abstract

Background. 

Understanding the interference patterns of respiratory viruses could be important for shedding light on potential strategies to combat these human infectious agents. 

Objective. 

To investigate the possible interactions between adenovirus type 2 (AdV2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/H1N1 pandemic (H1N1pdm09) using the A549 cell line. 

Methods. 

Single infections, co-infections, and superinfections (at 3 and 24 h after the first virus infection) were performed by varying the multiplicity of infection (MOI). Virus replication kinetics and the mRNA expression of IFN-α, IL-1α and IL-6 were assessed by real-time qPCR. 

Results. 

Co-infection experiments showed different growth dynamics, depending on the presence of the specific virus and time. AdV2 replication remained stable or possibly enhanced in the presence of co-infection with each of the two H1N1pdm09 and SARS-CoV-2 viruses used. In contrast, SARS-CoV-2 replication was facilitated by H1N1pdm09 but hindered by AdV2, indicating possible different interactions. Finally, H1N1pdm09 replication exhibited variably effectiveness in the presence of AdV2 and SARS-CoV-2. Superinfection experiments showed that the replication of all viruses was affected by time and MOI. The mRNA expression of IFN-α, IL-1α and IL-6 showed divergent results depending on the virus used and the time of infection. 

Conclusions. 

Further investigation of co-infection or superinfection may be helpful in understanding the potential relationship involved in the outcome of viral respiratory infection in the human population.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1947

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