The Effects of Swine Coronaviruses on ER Stress, Autophagy, Apoptosis, and Alterations in Cell Morphology

Abstract

Swine coronaviruses include the following six members, namely porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine delta coronavirus (PDCoV), swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine hemagglutinating encephalomyelitis virus (PHEV), and porcine respiratory coronavirus (PRCV). Clinically, PEDV, TGEV, PDCoV, and SADS-CoV cause enteritis, whereas PHEV induces encephalomyelitis, and PRCV causes respiratory disease. Years of studies reveal that swine coronaviruses replicate in the cellular cytoplasm exerting a wide variety of effects on cells. Some of these effects are particularly pertinent to cell pathology, including endoplasmic reticulum (ER) stress, unfolded protein response (UPR), autophagy, and apoptosis. In addition, swine coronaviruses are able to induce cellular changes, such as cytoskeletal rearrangement, alterations of junctional complexes, and epithelial-mesenchymal transition (EMT), that render enterocytes unable to absorb nutrients normally, resulting in the loss of water, ions, and protein into the intestinal lumen. This review aims to describe the cellular changes in swine coronavirus-infected cells and to aid in understanding the pathogenesis of swine coronavirus infections. This review also explores how the virus exerted subcellular and molecular changes culminating in the clinical and pathological findings observed in the field.

mTOR signaling regulates Zika virus replication bidirectionally through autophagy and protein translation

“…Autophagic vesicles were observed during SARS-CoV-2 or swine coronavirus infection and utilized for viral invasion and viral replication. 38,39 Surprisingly, knockdown of Atg5 or Atg7 during West Nile virus (WNV) infection inhibited autophagy but did not affect viral replication, suggesting that WNV replication was not regulated by the autophagy process and was different from that of other flaviviruses. 40,41 ZIKV infection of HUVECs dephosphorylated AKT but phosphorylated AMPK to inhibit mTORC1.…”

“…However, protein synthesis was hindered by dephosphorylation of S6K and 4E‐BP1, so viral protein expression and progeny release were limited. Autophagic vesicles were observed during SARS‐CoV‐2 or swine coronavirus infection and utilized for viral invasion and viral replication 38,39 . Surprisingly, knockdown of Atg5 or Atg7 during West Nile virus (WNV) infection inhibited autophagy but did not affect viral replication, suggesting that WNV replication was not regulated by the autophagy process and was different from that of other flaviviruses 40,41 …”

Clinical, Pathological and Virological Outcomes of Tissue-Homogenate-Derived and Cell-Adapted Strains of Porcine Epidemic Diarrhea Virus (PEDV) in a Neonatal Pig Model

“…These results could suggest that the degree of enterocyte damage is not strictly related to the amount of virus but depends on other factors. It has been recently demonstrated that different PCoV species, including PEDV, can modulate apoptosis, endoplasmic reticulum stress response and autophagy to favor a viral environment [ 12 ]. In the present study, both the PEDV-USA and CALAF-HOMOG strains showed evidence of enterocyte degeneration and death coinciding with areas of villous atrophy and fusion and the presence of viral antigen.…”

“…On the other hand, the viral factor that influences mostly the disease outcome is the ability of the different viral strains (S-INDEL or non-S INDEL) to evade the intestinal type I and III interferon (IFN) antiviral responses. Also, the virus exerts significant effects on the regulation of the main intercellular pathways linked to apoptosis, the endoplasmic stress response and autophagy [ 12 ].…”

Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection

“…For example, SARS-CoV-2 alters the structure of the ER to create replication sites, leading to ER stress and UPR activation [25]. In addition, swine coronaviruses like porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) can induce ER rearrangement and provoke ER stress [26]. Herein, we summarize the latest data concerning the crosstalk between coronavirus infection and UPR signaling, as well as the potential of therapeutically targeting the UPR against coronavirus infections.…”