The basis of complications in the context of SARS-CoV-2 infection: Pathological activation of ADAM17.

The virulence of SARS-CoV-2 decreases with increasing infectivity, the primary approaches for antiviral treatments will be preventing or minimizing the complications resulting from virus infection. ADAM metallopeptidase domain 17 (ADAM17) activation by SARS-CoV-2 infection has a dual effect on the development of the disease: increased release of inflammatory cytokines and dysregulation of Angiotensin converting enzyme II (ACE2) on cell surfaces, inflammatory cytokine infiltration and loss of ACE2 protective function lead to a significant increase in the incidence of related complications. Importantly, pathologically activated ADAM17 showed superior features than S protein in regulating ACE2 expression and participating in the intra cellular replication of SARS-CoV-2. In short, SARS-CoV-2 elicits only a limited immune response when it promotes its own replication and pathogenicity through ADAM17. Therefore, the pathological activation of ADAM17 may also represent a diminished innate antiviral defense and an altered strategy of SARS-CoV-2 infection. In this review, we summarized recent advances in our understanding of the pathophysiology of ADAM17, with a focus on the new findings that SARS-CoV-2 affects ADAM17 expression through Furin protein converting enzyme and Mitogen-activated protein kinase (MAPK) pathway, and raises the hypothesis that SARS-CoV-2 may mediates the pathological activation of ADAM17 by hijacking the actin regulatory pathway, and discussed the underlying biological principles.

Recombination and Mutation in a New HP-PRRSV Strain (SD2020) from China.

A new HP-PRRSV strain (SD2020) was isolated from pigs with suspected highly pathogenic porcine reproductive and respiratory syndrome disease in a pig farm in Shandong Province, China, and its genome was sequenced. This pig farm has been using the VR-2332 vaccine strain to immunize pigs for a long time. The phylogenic and single nucleotide polymorphisms (SNPs) analysis of the viruses isolated from dead pigs showed that SD2020 was a natural recombinant virus of the VR-2332 vaccine strain and the JXA1 similar strain, and that two splicing fragments highly homologous to JXA1 in the virus genome were probably derived from the JXA1 wild strain and JXA1-R vaccine strain, respectively. Therefore, the possible recombination events of SD2020 and its mutation site might be related to high pathogenicity.