Involvement of miR-15a in G0/G1 Phase Cell Cycle Arrest Induced by Porcine Circovirus Type 2 Replication.
Many viruses exploit the host cell division cycle to favour their own growth. Here we demonstrated that porcine circovirus type 2 (PCV2), which is a major causative agent of an emerging and important swine disease complex, PCV2-associated diseases, caused G0/G1 cell cycle arrest through degradation of cyclin D1 and E followed by reduction of retinoblastoma phosphorylation in synchronized PCV2-infected cells dependent upon virus replication. This induction of G0/G1 cell cycle arrest promoted PCV2 replication as evidenced by increased viral protein expression and progeny virus production in the synchronized PCV2-infected cells. To delineate a mechanism of miRNAs in regulating PCV2-induced G0/G1 cell cycle arrest, we determined expression levels of some relevant miRNAs and found that only miR-15a but not miR-16, miR-21, and miR-34a was significantly changed in the PCV2-infected cells. We further demonstrated that upregulation of miR-15a promoted PCV2-induced G0/G1 cell cycle arrest via mediating cyclins D1 and E degradation, in which involves PCV2 growth. These results reveal that G0/G1 cell cycle arrest induced by PCV2 may provide favourable conditions for viral protein expression and progeny production and that miR-15a is implicated in PCV2-induced cell cycle control, thereby contributing to efficient viral replication.
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, P. R. China.
Rong
R
Quan
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, P. R. China.
Li
L
Wei
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, P. R. China.
Shanshan
S
Zhu
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, P. R. China.
Jing
J
Wang
Life Sciences School, Sun Yat-sen University, Guangzhou Higher Education 11 Mega Center, Guangzhou 510006, P. R. China.
Yongchang
Y
Cao
Life Sciences School, Sun Yat-sen University, Guangzhou Higher Education 11 Mega Center, Guangzhou 510006, P. R. China.
Chunyi
C
Xue
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, P. R. China.
Xu
X
Yan
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, P. R. China.
Jue
J
Liu
D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002460:Cell Line; D018173:Circoviridae Infections / Q000235:genetics* / Q000473:pathology; D017925:Circovirus / Q000472:pathogenicity / Q000502:physiology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D013552:Swine; D015854:Up-Regulation; D014779:Virus Replication / Q000235:genetics*
D019927:Cyclin E; D035683:MicroRNAs; D019938:Cyclin D1