Schmallenberg virus induces apoptosis in Vero cell line via extrinsic and intrinsic pathways in a time and dose dependent manner

Abstract

Schmallenberg virus (SBV), discovered in 2011 in Germany, is associated with clinical manifestations of fever, diarrhea, reduced milk yield, abortions and congenital malformations in ruminants. Despite many studies performed for SBV, there is no detailed research on in vitro apoptotic effect of SBV. This study is aimed to determine apoptosis pathways and role of pro-apoptotic and anti-apoptotic molecules in Vero cells infected with SBV. The study results showed that SBV induced apoptosis via both extrinsic and intrinsic pathways by activating both caspase-8 and caspase-9, respectively. Expression analyses of pro-apoptotic ( Bax , Bak and Puma ) and anti-apoptotic ( Bcl-2 and Bcl-XL ) genes revealed that SBV-induced apoptosis causes upregulation of pro-apoptotic genes, dominantly via Puma gene, whereas Bcl-2 and Bcl-XL genes were downregulated. In conclusion, this is the first detailed report about SBV induced apoptosis in the Vero cells via both extrinsic and intrinsic cascades and apoptosis induction is seem to be regulated by Puma .

The Role of Bcl-xL Protein in Viral Infections

“…SBV infects ruminants and causes hyperthermia and diarrhea and decreases milk supply. Symptoms of the infection include, but are not limited to, abortions and congenital anomalies such as hydranencephaly, scoliosis, brachygnathia, hydrocephalus, and arthrogryposis [ 122 , 123 , 124 ].…”

“…The most important question is its influence on infected cell viability. Aksoy and Azkur [ 123 ] have studied the impact of SBV on the apoptotic potential of Vero cells. The research revealed that SBV infection triggered the intrinsic and extrinsic apoptosis pathways.…”

“…The outcome suggested that, to some extent, the pro-apoptotic effect of SBV infection may be due to the change in the levels of Bcl-xL. Nevertheless, further studies are necessary to investigate the importance of Bcl-xL in SBV infection and pathogenesis [ 123 ].…”

D-dimer levels and lymphocyte counts as prognostic and predictive factors in patients with COVID-19

“…The explanation of this mechanism shall serve as a guide for the treatment of severe patients. Apoptosis of lymphocytes is regulated by pro and anti-apoptotic mechanisms through endogenous and exogenous factors (19).…”

Development and validation of SYBR Green- and probe-based reverse-transcription real-time PCR assays for detection of the S and M segments of Schmallenberg virus

“…SBV (strain F6; GenBank accessions KC355457–KC355459 represent sequences from the 3 segments of SBV), from the laboratory of Dr. Wim H. M. van der Poel (Wageningen Bioveterinary Research), was propagated in Vero cells at 37°C in 5% humidified CO 2 . SBV propagations were confirmed by RT-PCR with 382-469 primers 5 and a plaque titration 1 assay (Suppl. Fig.…”