Defining Parameters That Modulate Susceptibility and Protection to Respiratory Murine Coronavirus MHV1 Infection

J Immunol. 2023 Dec 27:ji2300434. doi: 10.4049/jimmunol.2300434. Online ahead of print.ABSTRACTPatients infected with SARS-CoV-2 experience variable disease susceptibility, and patients with comorbidities such as sepsis are often hospitalized for COVID-19 complications. However, the extent to which initial infectious inoculum dose determines disease outcomes and whether this can be used for immunological priming in a genetically susceptible host has not been completely defined. We used an established SARS-like murine model in which responses to primary and/or secondary challenges with murine hepatitis virus type 1 (MHV-1) were analyzed. We compared the response to infection in genetically susceptible C3H/HeJ mice, genetically resistant C57BL/6J mice, and genetically diverse, variably susceptible outbred Swiss Webster mice. Although defined as genetically susceptible to MHV-1, C3H/HeJ mice displayed decreasing dose-dependent pathological changes in disease severity and lung infiltrate/edema, as well as lymphopenia. Importantly, an asymptomatic dose (500 PFU) was identified that yielded no measurable morbidity/mortality postinfection in C3H/HeJ mice. Polymicrobial sepsis induced via cecal ligation and puncture converted asymptomatic infections in C3H/HeJ and C57BL/6J mice to more pronounced disease, modeling the impact of sepsis as a comorbidity to β-coronavirus infection. We then used low-dose infection as an immunological priming event in C3H/HeJ mice, which provided neutral...

Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Elvia E Silva Steven J Moioffer Mariah Hassert Roger R Berton Matthew G Smith Stephanie van de Wall David K Meyerholz Thomas S Griffith John T Harty Vladimir P Badovinac Source Type: research