Table 1.
A synopsis of the apoptotic pathways induced by animal CoVs discussed in this review.
| Coronavirus | Strain | In Vitro/In Vivo | Apoptotic Pathway | Ref. |
|---|---|---|---|---|
| Alphacoronaviruses | ||||
|
PEDV
Host: swine |
SM98-1 | Vero Tissue specimens from duodenum, jejunum and ileum |
↑AIF | [30] |
| AJ1102 | Vero | 12 apoptotic proteins | [31] | |
| 8aa and KD | Vero | caspase 6 or 7 | [32] | |
| CV777 or SM98 | Vero, Vero-E6, and Marc-145 cells | ↑caspase-3, ↑caspase-8, AIFM1 and PARP cleavage |
[33] | |
| Shaanxi | Vero | ↑ p53, ↑ ROS | [34] | |
| DR13, CV777, rDR13att-ORF3CV777 rDR13att-ORF3NY rDR13att-∆ORF3 |
LR7, Vero CCL-81 | ↓caspase-3 Cleavage |
[35] | |
| CH/SXYL/2016 | Vero | G0/G1 arrest, ↑p53 | [36] | |
| CV777 | Vero, immortalized pig small intestinal mucosal epithelial cells | ↑apoptosis | [37] | |
| YC2014, CV777 | IPEC-J2 | ↑JAK-STAT, ↑NF-kB ↓PI3K-AKT/mTOR |
[38] | |
| CV777 | IPEC-J2 | ↓PI3K/Akt ↑mTOR upstream regulators (ATP6V1G1, FZD2 and LAMTOR2), ↑ PTEN |
[39] | |
|
TGEV
Host: swine |
Shaanxi | PK-15 | ↓p300/CBP, ↓MDM2 ↑p53, p38 MAPK |
[28] |
| Shaanxi | PK-15 | ↑ROS, ↑p53, p38 MAPK | [45] | |
| Shaanxi | PK-15 | ↑AIFM1, PARP cleavage, ↑ROS | [46] | |
| Shaanxi | PK-15 | ↑Fas/FasL, ↑Bid, ↑Bax, ↓Bcl-2 ↑ cleaved PARP, ↑caspase 8,9,3 |
[47] | |
| Shaanxi | PK-15 | S and G2/M cycle arrest ↑p53, ↑p21 |
[48] | |
| Purdue-11 | HRT18 | caspase 3,6,7,8,9 | [49] | |
| Shaanxi | PK-15 | miR-27b, ↓RUNX1 ↓Bax, caspase 3,9 |
[50] | |
|
SADS-CoV
Host: swine |
SADS-CoV | Vero, IPI-2I | ↑ Fas/FasL ↑ caspase 8,9, 3, PARP cleavage |
[52] |
|
FECV
Host: Feline (cat) |
79-1146 | Feline peripheral blood mononuclear cells (PBMC), CD4+ cells, CD8+ cells, CD21+ cells, peritoneal exudate cells (PEC), alveolar macrophages, and WEHI-164 murine sarcoma cells | ↑TNF-α | [56] |
| 79–1146 | CRFK | ↑PDL1 | [57] | |
| FIPV-m3c-2 | Peritoneal cells | ↑ Fas, TNF, Bax, Bak, Bix, Bid, Traf2 | [58] | |
| FIPV 79-1146 | CRFK | ↓TNF, TGFbeta, STAT3 | [59] | |
| FIPV 79-1146 | CRFK | p53, p38 MAPK, VEGF | [60] | |
|
CCoV
Host: Canine (dog) |
Type I, 1–71 | A-72 | ↑ caspase 3 | [63] |
| Type II, S/378 | A-72 | PARP, Bid cleavage ↑ caspase 8,9,3,6 |
[64] | |
| Type II, S/378 | A-72 | ↑TRAIL, ↑ Fas/FasL, ↓Bcl-2 | [67] | |
| Betacoronaviruses | ||||
|
MHV
Host: mouse |
A59 | 17Cl-1 | caspase dependent | [78] |
| MHV-3 | A/J and BALB/c macrophages | fgl2 prothrombinase | [79] | |
| MHV-3 | BTLA-deficient (BTLA-/-) mice | TRAIL | [81] | |
| A59 | oligodendrocytes | apoptosis | [84] | |
| JHM | CG-4 | ↑Fas/FasL/FADD/procaspase 8 | [103] | |
| MHV-2 | thymus | apoptosis | [86] | |
|
PHEV
Host: swine |
HEV-67N | PK-15 | ↑ Fas/FasL ↑ caspase 8,9, 3, PARP cleavage |
[90] |
| 67Ν | Four- to six-week-old female BALB/c mice | ↑bak1, ↑caspase 1,3,4,7,8,12 |
[91] | |
|
ECoV
Host: horse |
NC99 | MDBK | ↑caspase 3,7,8,9 | [94] |
| Gammacoronaviruses | ||||
|
IBV
Host: avian |
Beaudette | Vero | ↑ caspase 3, ↑ cleaved PARP | [99] |
| Beaudette | Vero | p53 independent | [100] | |
| Beaudette | Vero | ↑ Bak | [101] | |
| ck/CH/LDL/091022 | Chicken kidney tissue | ↑Bcl2, Fas, ↓clusterin | [102] | |
| SCDY2 SCK2 |
Chicken kidney tissue | BCL2L1, GADD45, STAT3 |
[103] | |
| Beaudette | Vero | ↑ PERK, PKR, ATF3, ATF4, GADD153, TRIB3,↓ Bcl2, ERKs | [104] | |
| Beaudette | Vero, H1299, Huh-7 | ↑ MKK7, JNK, ↓Bcl-2 | [105] | |
| Beaudette | Vero, H1299 | ↑ ERK1/2, ↑cJUN, JUNB, JUND, cFOS, FOSB | [106] | |
| Beaudette | Vero | PARP cleavage | [107] | |
| Beaudette | macrophage HD11 | ↑ Fas/FasL,↑ caspase 8,9, 3 ↓Bcl-2 |
[108] | |
| Deltacoronaviruses | ||||
|
PDCoV
Host: swine |
KNU16-07 | ST cells | Bax, cytochrome C, caspase 9 | [112] |
| CH/XJYN/2016 | LLC-PK | ↑ caspase 8,7,3, ↓ PARP | [113] | |