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Viruses ; 14(5)2022 05 15.
Article in English | MEDLINE | ID: covidwho-1884377


In this study, we investigated the correlation between the mechanism involved in porcine epidemic diarrhea virus (PEDV) replication and autophagic flux. In this study, we found that as PEDV replicated, production of LC3-II was significantly induced up to 24 h post-infection (hpi). Interestingly, although there was significant production of LC3-II, greater p62 accumulation was simultaneously found. Pretreatment with rapamycin significantly induced PEDV replication, but autolysosome formation was reduced. These results were confirmed by the evaluation of ATG5/ATG12 and LAMP1/LAMP2. Taken together, we conclude that PEDV infection induces autophagosome formation but inhibits autolysosome formation during replication.

Autophagosomes/metabolism , Porcine epidemic diarrhea virus , Animals , Autophagosomes/genetics , Chlorocebus aethiops , Lysosomes/genetics , Lysosomes/metabolism , Macroautophagy , Porcine epidemic diarrhea virus/immunology , Swine , Vero Cells
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Article in English | MEDLINE | ID: covidwho-1238060


COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.

Antigen Presentation , COVID-19/immunology , Down-Regulation/immunology , Histocompatibility Antigens Class I/immunology , Immune Evasion , SARS-CoV-2/immunology , Viral Proteins/immunology , Animals , Autophagy/genetics , Autophagy/immunology , COVID-19/genetics , Chlorocebus aethiops , HEK293 Cells , Histocompatibility Antigens Class I/genetics , Humans , Lysosomes/genetics , Lysosomes/immunology , Lysosomes/virology , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells , Viral Proteins/genetics
Mol Genet Metab ; 132(2): S2-S6, 2021 02.
Article in English | MEDLINE | ID: covidwho-1091577