SERTA Domain Containing Protein 1 (SERTAD1) Interacts with Classical Swine Fever Virus Structural Glycoprotein E2, Which Is Involved in Virus Virulence in Swine

Abstract

E2 is the major structural glycoprotein of the classical swine fever virus (CSFV). E2 has been shown to be involved in important virus functions such as replication and virulence in swine. Using the yeast two-hybrid system, we previously identified several host proteins specifically interacting with CSFV E2. Here, we analyze the protein interaction of E2 with SERTA domain containing protein 1 (SERTAD1), a factor involved in the stimulation of the transcriptional activities of different host genes. We have confirmed that the interaction between these two proteins occurs in CSFV-infected swine cells by using a proximity ligation assay and confocal microscopy. Amino acid residues in the CSFV E2 protein that are responsible for mediating the interaction with SERTAD1 were mapped by a yeast two-hybrid approach using a randomly mutated E2 library. Using that information, a recombinant CSFV mutant (E2ΔSERTAD1v) that harbors substitutions in those residues mediating the protein-interaction with SERTAD1 was developed and used to study the role of the E2-SERTAD1 interaction in viral replication and virulence in swine. CSFV E2ΔSERTAD1v, when compared to the parental BICv, showed a clearly decreased ability to replicate in the SK6 swine cell line and a more severe replication defect in primary swine macrophage cultures. Importantly, 80% of animals infected with E2ΔSERTAD1v survived infection, remaining clinically normal during the 21-day observational period. This result would indicate that the ability of CSFV E2 to bind host SERTAD1 protein during infection plays a critical role in virus virulence.

Exploring the Role of TRIP-Brs in Human Breast Cancer: An Investigation of Expression, Clinicopathological Significance, and Prognosis

“…Apart from these, the potential roles of TRIP-Brs in BRCA and other cellular processes through several biological pathways, including E2F1 proliferation pathway, neurological process, PI3K/AKT/BRCA1 axis signaling pathway, 56 adenylyl cyclase-mediated cAMP signaling, 12 Nrf pathway, 26 ER stress-induced BAT dysfunction, 57 , 58 BMP/SMAD pathway, 58 reactive oxygen species (ROS)-induced cell death and ubiquitination, 11 , 15 p53 transcriptional and pRb1-cyclin D1-cdk4/6-p16(INK4A) pathway, 59 Toll-like receptor (TLR), induced immune. 18 , 27 , 60 , 61 , 62 Further, this study also revealed the correlation between mRNA levels of TRIP-Brs and immune-infiltrating factors. Thus, TRIP-Brs may also play an essential role in spatial heterogeneity of the tumor microenvironment in patients with BRCA.…”

Inverted terminal repeats from adeno-associated virus-2 enhance the expression of the chimeric E2 glycoprotein gene of classical swine fever virus

“…Besides, it has been shown that E2 can interact with a wide range of host proteins such as actin, thiredoxin, an-nexin 2, dynactin 6, mitogen-activated protein kinase 2, SERTA domain containing protein 1, etc. [22]. The data obtained by FACS-analysis revealed that the number of cells with a high fluorescence intensity was significantly higher in pTR-EGFP/E2 transfected cells 41.9±13.1 % (of the total cell number) (Fig.…”

A β-Hairpin Motif in the Envelope Protein E2 Mediates Receptor Binding of Bovine Viral Diarrhea Virus

“…Porcine cell lines that do not express CD46 were shown to be non-permissive to APPV infection, while porcine pestiviruses such as CSFV and BuPV efficiently infected these cells, indicating a CD46-independent mechanism of entry [ 15 ]. Additional binding partners of CSFV E2 have been identified and mapping of amino acids involved in these interactions has been achieved using yeast-two hybrid system [ 32 , 33 , 34 ]. These factors do not appear to play a role in virus entry, and the regions involved in these interactions fall outside the β-hairpin motif in domain II.…”