Nature: Use K18-hACE2 mice to evaluate COVID-19...

Like severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), SARS-CoV-2 uses the same subject, human angiosin conversion enzyme 2 (hACE2), to enter human cells.
mice were susceptible to SARS-CoV, but they were resistant to SARS-CoV-2 infection due to incompatibness between ACE2 and SARS-CoV-2 prickly protein (S protein).
during the SARS epidemic of 2003-2004, infected mice developed only mild disease, so researchers at the University of Iowa and others built genetically modified mice (K18-hACE2 mice) that expressed hACE2.
K18-hACE2 mice expressed hACE2, driven by the initiator of the cell keratin 18 encoded gene, mainly in endotrine cells.
both SARS-CoV-2 and SARS-CoV used hACE2, but differences were shown in patients' disease manifestations, with SARS-CoV-2 infecting the upper respiratory tract to a greater extent than SARS-CoV.
SARS-CoV-2 has been associated with clinical manifestations such as loss of smell, loss of taste, thrombosis and endosperm damage to the pulmonary vascular endoskines, heart and nervous system diseases, and multisyscillar inflammation in children and adolescents.
these observations, researchers at the University of Iowa concluded that mice infected with SARS-CoV-2, K18-hACE2, may also show differences in pathogenesis.
a new study, Paul B. McCray Jr. and Stanley Perlman of the University of Iowa and colleagues demonstrated the effectiveness of K18-hACE2 mice in the study and treatment of COVID-19 disease.
they found that SARS-CoV-2 infection with K18-hACE2 mice causes dose-dependent fatal respiratory diseases characterized by severe human COVID-19, including diffuse alva damage, inflammatory cell immersion, tissue damage, pulmonary vascular damage, and death, some of which can result in brain infections.
results were recently published in the journal Nature under the title "COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice".
hACE2 genetically modified mice, which are also driven by other starters, have also been developed and different results have been observed after SARS-CoV-2 infection.
notably, K18-hACE2 mice also support sinus endotent SARS-CoV-2 replication and loss of sense of smell after this viral infection, a common feature of COVID-19.
addition, K18-hACE2 mice inoculated with 105 PFU SARS-CoV-2 using recovery plasma pre-treatment from COVID-19 patients prevented them from contracting fatal disease outcomes.
, it is important to note that recovery plasma pre-treatment does not prevent initial infections of the lungs, damage to the nasal respiratory tract and olfactory overdit, and loss of sense of smell.
the authors observed a greater loss of sense of smell in female mice than in male mice, regardless of whether they received pre-treatment of plasma during recovery.
, female patients had a more common loss of sense of smell than men with COVID-19.
SARS-CoV-2-infected K18-hACE2 mice treated with recovery plasma or potentially meso-monoclonal antibodies will be particularly useful for studying olfactory loss, which is usually less susceptible to SARS-CoV-2 infection in mice, but like many patients with mild infections.
loss of sense of smell appears to be the result of the initial infection and damage to the strut cells, rather than damage to the olfactory sensory neurons, suggesting that the resulting inflammatory environment, rather than direct neuronal damage, is the cause of the disease.
, the authors speculate that there are at least two possible explanations for the observed loss of sense of smell.
, infection of strut cells can disrupt signaling from olfactory sensory neurons (OSNs) to olfactory balls.
, for example, pillar cells support OSN by maintaining ion balance, which may change directly through strut cell infection or indirectly through olfactory superseed destruction, resulting in loss of cile hair from OSN and signal transductivity defects.
second possibility is that OSN is collateral damage caused by inflammatory cytokines secreted by strut cells infected with SARS-CoV-2.
in patients with chronic sinusitis and COVID-19, these cells have been reported to secrete cytokines such as TNF, Il-1 beta, Il-1 alpha, and CXCL2.
In summary, MICE-CoV-2-infected K18-hACE2 mice reproduced many of the findings observed in COVID-19 patients, thus providing a useful model for studying pathogenesis and evaluating interventions.
reference: Jian Zheng et al. COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice. Nature, 2020, doi:10.1038/s41586-020-2943-z. This article is sourced from Bio Valley, for more information please download Bio Valley APP (