SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation

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 binding 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 demonstrate 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.

Insect-specific viruses in the Parvoviridae family: Genetic lineage characterization and spatiotemporal dynamics of the recently established Brevihamaparvovirus genus

“…The NS proteins share the majority of conserved domains and a coiled region essential for DNA replication (Bergoin and Tijssen, 2010). The regions encoding NS1 and NS2 overlap, but each protein is encoded from a distinct reading frame after alternative splicing (Chen et al, 2021). While two of the regions displayed high phylogenetic signal (NS1 and VP), only one revealed a strong temporal signal (VP-coding region) required for spatiotemporal dispersal analysis.…”

“…Among parvoviruses, the members of the genus Brevihamaparvovirus have some of the smallest ssDNA genomes (approximately 4 kb), with three open reading frames encoding two non-structural proteins (NS1, NS2) and a capsid protein (VP) (Bergoin and Tijssen, 2010). While NS1 has been known to be crucial for the initiation of viral DNA replication, NS2 participates in viral egress from the nucleus where viral replication takes place (Chen et al, 2021). The VP gene encodes a capsid protein that is essential for viral entry into host cells and the production of infectious virus (Sánchez-Martínez et al, 2012).…”

Epidemiology and molecular characterization of Feline panleukopenia virus from suspected domestic cats in selected Bangladesh regions

“…The FPL virus (FPLV) can infect both domestic and wild felids (suborder Feliformia), as well as a few wild canids (suborder Caniformia) such as raccoons and foxes. This virus does not infect domestic dogs [3,4]. FPLV belongs to the family Carnivore protoparvovirus-1and is a small, nonenveloped, linear, single-stranded DNA virus with a genome of 5.1-kb [5].…”

“…FPLV belongs to the family Carnivore protoparvovirus-1and is a small, nonenveloped, linear, single-stranded DNA virus with a genome of 5.1-kb [5]. The basic structure of the virus involves two non-structural proteins (NS1 and NS2) and two structural capsid proteins (VP1 and VP2) that are encoded by two open reading frames (ORFs) [3,4].…”