PMC:7324763 / 18085-20704 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7324763","sourcedb":"PMC","sourceid":"7324763","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7324763","text":"There is currently a paucity of studies into the role of NK cells not only in COVID-19 pathophysiology, but also in other coronavirus infections. An in vivo study reported that beige mice on a B6 background cleared SARS-CoV-1 normally, indicating that functional lymphocytes, including NK cells, may not be required to eliminate SARS-CoV-1 in murine models (119). However, in a more recent study characterizing the cellular immune response to SARS-CoV-1 in 12–14-month old BALB/c mice, T cell depletion did not prevent control of SARS-CoV-1 replication (120), suggesting a role for the innate immune system, and NK cells, in viral clearance. Importantly, in this study CD4-depletion resulted in enhanced lung immunopathology and delayed viral clearance, while CD8-depletion did not affect viral replication or clearance, thus highlighting an important role for CD4+ T cells in coronavirus infection. These conflicting results may be due to the inherent limitations of CoV murine models. In 4–8 week-old mice, SARS-CoV-1 is associated only with mild pneumonitis and cytokines are not detectable in the lungs (119, 121, 122). A SARS-CoV-1 isolate (MA-15) replicates to a high titer and is associated with viremia and mortality, however the model lacks significant inflammatory cell infiltration into the lungs (123). Thus, mouse models developed for the study of SARS fell short in terms of reproducing the clinical and histopathological signs of disease (119, 121–123). It is therefore necessary to develop a usable animal model that is capable of reproducing the clinical and histopathological signs on COVID-19. Israelow et al. recently described a SARS-CoV-2 murine model based on adeno associated virus (AAV)9-mediated expression of human (h)ACE2, which replicated the pathologic findings found in COVID-19 patients (124). This model, which overcame the inability of murine (m)ACE2 to support SARS-CoV-2 infection, was used to show the inability of Type I IFN to control SARS-CoV-2 replication (124). In a similar attempt to overcome the lack of infectability through mACE2, Dinnon et al. recently described a recombinant virus (SARS-CoV-2 MA) with a remodeled S protein mACE2 interface, which replicated in upper and lower airways in young and aged mice with disease being more severe in aged mice. The authors used this model to screen therapeutics from vaccine challenge studies and assessed pegylated IFN-λ-1 as a promising therapeutic. The authors suggested that this model has greater ease of use, cost, and utility over transgenic hACE2 models (125) to evaluate vaccine and therapeutic efficacy in mice 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