Syncrip facilitates porcine parvovirus viral dna replication through the alternative splicing of ns1 mrna to promote ns2 mrna formation

Chen et al. Vet Res (2021) 52:73
https://doi.org/10.1186/s13567-021-00938-6
RESEARCH ARTICLE
SYNCRIP facilitates porcine parvovirus viral 
DNA replication through the alternative splicing 
of NS1 mRNA to promote NS2 mRNA formation
Songbiao Chen
†
, Bichen Miao
†
, Nannan Chen, Caiyi Chen, Ting Shao, Xuezhi Zhang, Lingling Chang, 
Xiujuan Zhang, Qian Du, Yong Huang
*
and Dewen Tong
*

Abstract 
Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and 
VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after 
alternative splicing, yet the corresponding mechanism is unclear. In this study, we identified a PPV NS1 mRNA bind-
ing protein SYNCRIP, which belongs to the hnRNP family and has been identified to be involved in host pre-mRNA 
splicing by RNA-pulldown and mass spectrometry approaches. SYNCRIP was found to be significantly up-regulated 
by PPV infection in vivo and in vitro. We confirmed that it directly interacts with PPV NS1 mRNA and is co-localized 
at the cytoplasm in PPV-infected cells. Overexpression of SYNCRIP significantly reduced the NS1 mRNA and protein 
levels, whereas deletion of SYNCRIP significantly reduced NS2 mRNA and protein levels and the ratio of NS2 to NS1, 
and further impaired replication of the PPV. Furthermore, we found that SYNCRIP was able to bind the 3
′-terminal site 
of NS1 mRNA to promote the cleavage of NS1 mRNA into NS2 mRNA. Taken together, the results presented here dem-
onstrate that SYNCRIP is a critical molecule in the alternative splicing process of PPV mRNA, while revealing a novel 
function for this protein and providing a potential target of antiviral intervention for the control of porcine parvovirus 
disease.