Table 1.
Effect of the proteasome on the propagation of viral particles.
| Virus | Cell type | Treatment/condition | Effect on viral replication | Targeted step in life cycle of virus | References |
|---|---|---|---|---|---|
| Adenovirus | HeLa cells | MG132 | Reduced | Late gene expression | (69) |
| Mouse adenovirus1 | C57BL/6 mice | LMP7−/− | No effect | n.r. | (31) |
| Coxsackie-virus B3 (CVB3) | Murine myxoma cell line HL-1 | MG132, lactacystin | Reduced | Post entry | (70) |
| A/J mice | MLN353 | No effect | n.r. | (71) | |
| C57BL/6 mice | LMP7−/− | No effect | n.r. | (23) | |
| Murine embryonic cardiomyocytes | ONX 0914 | No effect | n.r. | (72) | |
| C57BL/6 mice | ONX 0914 | Increased cardiac titers | |||
| A/J mice | ONX 0914 | No effect on cardiac titers | |||
| HeLa cells | PA28α/β siRNA | Increased | n.r. | (73) | |
| HeLa cells | PA28α/β overexpression | Reduced | |||
| Murine embryonic cardiomyocytes | PA28α/β−/− | Increased | |||
| C57BL/6 mice | PA28α/β−/− | No effect on cardiac titers | |||
| Herpes simplex virus 1 (HSV-1) | Monkey kidney epithelial cells (Vero cells) Hamster ovary cells (CHO-cells) |
MG132 epoxomicin lactacystin | Reduced | Virus entry/post penetration step | (74) |
| HeLa derivative HEp-2 | MG132, MG115, epoxomicin | Reduced | Immediate-early and late viral proteins | (75) | |
| Human cytomegalo-virus (HCMV) | Human embryonic lung fibroblasts | MG132 | Reduced | All stages of viral replication | (76) |
| Human embryonic lung fibroblasts | MG132 | Reduced | Immediate early protein synthesis | (77) | |
| Human immuno-deficiency virus 1/2 (HIV1/2) | HeLa cells, human T cell line A3.01 | MG132, lactacystin | Reduced | Gag processing and virus particle release | (78) |
| Human CD4+ T cells, human CD4+ cell line OM-10.1 | Bortezomib, lactacystin, MG132 | Reduced | Infectivity of the virion and viral latency | (79) | |
| Influenza A virus | Canine kidney cells MDCK | MG132, bortezomib | Reduced | Post fusion | (80) |
| Minute virus of mice1 | Murine B cells A9 | MG132, lactacystin, epoxomicin | Reduced | Post endosomal escape | (81) |
| Polio virus | HeLa cells | MG132, bortezomib | Reduced | Post entry (no effect on translation) | (82) |
| Vaccinia virus | HeLa cells | MG132, epoxomicin | Reduced | Post entry (viral genome replication; intermediate and late gene expression) | (83) |
| HeLa cells | MG132, bortezomib | Reduced | Genome uncoating, replication, late viral gene expression, virus assembly | (84) |
The table summarizes viruses with known cardiac tropism and the impact of different proteasome inhibitors (bortezomib, MG132, lactacystin, MLN353, MG115, as well as, the immunoproteasome-selective inhibitor ONX 0914 (59)), of the proteasome activator PA28 (85), as well as, of the i-proteasome (cell culture and mouse studies using LMP7−/− mice or cell lines obtained from these mice (47) on viral replication. CHO, chinese hamster ovary; MDCK, madin-darby canine kidney; Gag, group-specific antigen; n.r., not reported; MLN353, Millennium353 (proteasome inhibitor); ONX 0914, immunoproteasome-specific inhibitor; PA28α/β, proteasome activator α/β of 28 kDa.
1
Murine pathogens.