Bta-miR-98 Suppresses Replication of Caprine Parainfluenza Virus Type 3 Through Inhibiting Apoptosis by Targeting Caspase-3

Abstract

Caprine parainfluenza virus type 3 (CPIV3) is an emerging respiratory pathogen that affects the sheep and goat industry in China and possibly other countries around the world. Accumulating evidence suggests that microRNAs play important roles in regulating virus-host interactions and can suppress or facilitate viral replication. In this study, we showed that CPIV3 infection induced apoptosis in Madin-Darby bovine kidney (MDBK) cells, as determined by morphological changes and flow cytometry. Caspase activity and the expression of pro-apoptotic genes further indicated that CPIV3 induced apoptosis by activating both the intrinsic and extrinsic pathways. We also demonstrated the involvement of bta-microRNA-98 (bta-miR-98) in regulating CPIV3-induced apoptosis. Bta-miR-98 was downregulated in MDBK cells infected with CPIV3. Overexpression of bta-miR-98 significantly decreased the activities of caspase-3, −8, and −9. Conversely, inhibition of bta-miR-98 had completely opposite effects. Furthermore, our data showed that bta-miR-98 markedly affected CPIV3 replication by regulating apoptosis. Importantly, we found that bta-miR-98 modulated CPIV3-induced apoptosis by targeting caspase-3, an effector of apoptosis. Collectively, our results may suggest that CPIV3 infection induced apoptosis and downregulated the levels of bta-miR-98, and this miRNA regulated viral replication through effected apoptosis. This study contributes to our understanding of the molecular mechanisms underlying CPIV3 pathogenesis.

The evaluation of both the expression and serum protein levels of Caspase‐3 gene in patients with different degrees of SARS‐CoV2 infection

“…13 In addition, the Caprine parainfluenza virus type 3, an emerging respiratory pathogen, triggers apoptosis by targeting CASP3, an effector of apoptosis. 14 In our study, we found a significant relationship between CASP3 Studies reported that as HB 16,17 and lymphocyte 18…”

“…Also, CASP3 , 8 and 9 activities and the interferon promoter terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling were strongly induced in early infection in H5N1 Cambodia PA‐infected cells that protect uninfected cells from viral infection 13 . In addition, the Caprine parainfluenza virus type 3, an emerging respiratory pathogen, triggers apoptosis by targeting CASP3 , an effector of apoptosis 14 …”

“…Both past and present studies about the relationship between the CASP3 gene and various viral infections, such as Enterovirus 71 (EV71), [7][8][9] parvovirus H1, 10 human cytomegalovirus, 11 hepatitis C virus, 12 H5N1 Cambodia PA virus, 13 Caprine parainfluenza virus type 3, 14 and others have been performed. However, to the best of our knowledge, no studies have been conducted about the expression levels and functions of nucleolin on CASP3 gene expression in patients with different degrees of cellular injury caused by SARS-CoV-2 infection who had mild illness and healed from the disease and those with mild disease, moderate, severe, and critical illness.…”

RETRACTED: Non-coding RNA in SARS-CoV-2: Progress toward therapeutic significance

“…Using dual-luciferase reporter assay, bta-miR-98 was observed to act with Caspase-3. Through overexpression of bta-miR-98, caspase-3 signaling was inhibited, leading to lower apoptosis and suppression of CPIV3 replication [37] . Additionally, X Fei et al examined regulatory alterations on proliferation, migration, invasion, and apoptosis of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) caused by miR-98.…”

Research Progress on Emerging Viral Pathogens of Small Ruminants in China during the Last Decade

“…(2) Inducing apoptosis: CPIV3 infection induces apoptosis in both MDBK cells and goat tracheal epithelial cells by activating both the intrinsic and extrinsic pathways, which subsequently increases CPIV3 replication. Mechanistically, the ability of CPIV3 to induce apoptosis is mediated by the N protein [74,75]. One of the host cellular miRNAs, bta-miR-98, which markedly reduces CPIV3 replication by regulating apoptosis, is downregulated during CPIV3 infection and promotes viral replication.…”