Porcine ISG15 fused IFN-λ3 as a novel antiviral agent for treating porcine reproductive and respiratory syndrome virus infection in vivo.

IFN-λs hold promise as therapeutic candidates against mutable respiratory viruses, but their efficacy against porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. In this study, we expressed a recombinant fusion protein consisting of porcine ISG15 linked porcine IFN-λ3 (ISG15-IFN-λ3) via a rigid protein linker in Escherichia coli (E. coli).

A Broad-specificity Neutralizing Nanobody against Hepatitis E Virus Capsid Protein.

Hepatitis E virus (HEV) is a worldwide zoonotic and public health concern. The study of HEV biology is helpful for designing viral vaccines and drugs. Nanobodies have recently been considered appealing materials for viral biological research.

Porcine HERC6 acts as major E3 ligase for ISGylation and is auto-ISGylated for effective ISGylation in porcine.

Interferon-stimulated gene product 15 (ISG15) can be conjugated to substrates through ISGylation. Currently, the E3 ligase for porcine ISGylation remains unclear. Here, we identified porcine HERC5 and HERC6 (pHERC5/6) as ISGylation E3 ligases with pHERC6 acting as a major one by reconstitution of porcine ISGylation system in HEK-293 T cell via co-transfecting E1, E2 and porcine ISG15(pISG15) genes.

Characterization of in vitro viral neutralization targets of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) in alveolar macrophage and evaluation of protection potential against HP-PRRSV challenged based on combination of HP-PRRSV-structure proteins in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global pork industry, resulting in substantial economic losses. Current control measures rely on modified live virus (MLV) vaccines with safety concerns. However, the lack of consensus on protective PRRSV antigens is impeding the development of effective and safety subunit vaccines.

A nanobody inhibiting porcine reproductive and respiratory syndrome virus replication via blocking self-interaction of viral nucleocapsid protein.

Porcine reproductive and respiratory syndrome (PRRS) is a serious global pig industry disease. Understanding the mechanism of viral replication and developing efficient antiviral strategies are necessary for combating with PRRS virus (PRRSV) infection. Recently, nanobody is considered to be a promising antiviral drug, especially for respiratory viruses.

The PRMT5/WDR77 complex restricts hepatitis E virus replication.

Hepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we aimed to identify the host factors regulating HEV replication.

Decreased expression of HBV surface antigen (HBsAg) with sK122R and sV96A co-mutation is associated with an ineffective antibody response in a chronic hepatitis B patient.

Background: Emergence and predominance of hepatitis B virus (HBV) variants carrying S gene mutations frequently occur in HBV-infected individuals. Here, coexistent serum anti-HBsAg antibody (HBsAb) and HBV surface antigen (HBsAg) were detected in a chronic HBV patient. The patient's HBsAg proteins possessed amino acid substitutions sK122R and sV96A.

Identification of two novel neutralizing nanobodies against swine hepatitis E virus.

Hepatitis E virus (HEV) is thought to be a zoonotic pathogen that causes serious economic loss and threatens human health. However, there is a lack of efficient antiviral strategies. As a more promising tool for antiviral therapy, nanobodies (also named single-domain antibodies, sdAbs) exhibit higher specificity and affinity than traditional antibodies.

A simple nanobody-based competitive ELISA to detect antibodies against African swine fever virus.

African swine fever virus (ASFV) infection is a big threat to the global pig industry. Because there is no effective vaccine, rapid, low-cost, and simple diagnosis methods are necessary to detect the ASFV infection in pig herds. Nanobodies, with advantages of small molecular weight and easy genetic engineering, have been universally used as reagents for developing diagnostic kits.

A porcine reproductive and respiratory syndrome virus (PRRSV)-specific IgM as a novel adjuvant for an inactivated PRRSV vaccine improves protection efficiency and enhances cell-mediated immunity against heterologous PRRSV challenge.

Current strategies for porcine reproductive and respiratory syndrome (PRRS) control are inadequate and mainly restricted to immunization using different PRRS virus (PPRSV) vaccines. Although there are no safety concerns, the poor performance of inactivated PRRSV vaccines has restricted their practical application. In this research, we employed the novel PRRSV-specific IgM monoclonal antibody (Mab)-PR5nf1 as a vaccine adjuvant for the formulation of a cocktail composed of inactivated PRRSV (KIV) and Mab-PR5nf1 along with a normal adjuvant to enhance PRRSV-KIV vaccine-mediated protection and further compared it with a normal KIV vaccine and modified live virus vaccine (MLV).

Formation and Transfer of Multi-Species Biofilms Containing O103:H2 on Food Contact Surfaces to Beef.

Interactions of Shiga toxin-producing (STEC; O103:H2) with lactic acid bacteria (LAB) or spoilage bacteria (SP) multispecies biofilms on polyurethane (TPU) and stainless-steel (SS) were assessed at 10 and 25°C under wet and dry conditions after 6, 30, and 60 days of storage. One LAB T1: + , and two SP T2: + T3: + were assessed for their ability to form multispecies biofilms with O103:H2. O103:H2 single-species biofilms served as a control positive (T4).

Ovarian Oxidative Stress Induced Follicle Depletion After Zona Pellucida 3 Vaccination Is Associated With Subfertility in BALB/c Mice.

Impaired follicular development associated with autoimmune ovarian disease (AOD), is a typical side effect of ZP3 vaccine-induced subfertility and contributes to the fertility decline, but the mechanism is unknown. In this study, a AOD model was established with recombinant mouse zona pellucida 3 (mZP3) protein in the BALB/c mice, and co-administrated with 0.5 mg/kg antioxidant stress drug sodium selenite (SS), whereas intraperitoneal injection was used and the relationships among oxidant stress (OS), follicle loss and fertility were evaluated.

Avian Hepatitis E Virus ORF2 Protein Interacts with Rap1b to Induce Cytoskeleton Rearrangement That Facilitates Virus Internalization.

Avian hepatitis E virus (HEV) causes liver diseases and multiple extrahepatic disorders in chickens. However, the mechanisms involved in avian HEV entry remain elusive. Herein, we identified the RAS-related protein 1b (Rap1b) as a potential HEV-ORF2 protein interacting candidate.

Porcine Epidemic Diarrhea Virus Envelope Protein Blocks SLA-DR Expression in Barrow-Derived Dendritic Cells by Inhibiting Promoters Activation.

Porcine epidemic diarrhea (PED) is an acute, highly contagious intestinal swine disease caused by porcine epidemic diarrhea virus (PEDV). In addition to known PEDV infection targets (villous small intestinal epithelial cells), recent reports suggest that dendritic cells (DCs) may also be targeted by PEDV . Thus, in this study we used bone marrow-derived dendritic cells (BM-DCs) as an model of antigen-presenting cells (APCs).

Cell Division Control Protein 42 Interacts With Hepatitis E Virus Capsid Protein and Participates in Hepatitis E Virus Infection.

Hepatitis E Virus (HEV) causes viral hepatitis in humans worldwide, while a subset of HEV species, avian HEV, causes hepatitis-splenomegaly syndrome in chickens. To date, there are few reports on the host proteins interacting with HEV and being involved in viral infection. Previous pull-down assay combining mass spectrometry indicated that cell division control protein 42 (CDC42), a member belonging to the Rho GTPase family, was pulled down by avian HEV capsid protein.

Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient: A case report.

Background: Hepatocellular carcinoma (HCC) may be caused by hepatitis B virus (HBV) infection. Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen (HBsAg) level and increased anti-HBsAg antibody titer. Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC development.

The Hepatitis E Virus Open Reading Frame 2 Protein: Beyond Viral Capsid.

Hepatitis E virus (HEV) is a zoonotic pathogen causing hepatitis in both human and animal hosts, which is responsible for acute hepatitis E outbreaks worldwide. The 7.2 kb genome of the HEV encodes three well-defined open reading frames (ORFs), where the ORF2 translation product acts as the major virion component to form the viral capsid.

Development of a competitive ELISA for detecting antibodies against genotype 1 hepatitis E virus.

Hepatitis E, a significant global public health issue in China, is caused by sporadic infections with regional hepatitis E virus (HEV) genotypes 1, 3, and 4. To date, most immunoassays currently used to test human sera for the presence of anti-HEV antibodies cannot identify HEV at the genotype level. However, such information would be useful for identifying the source of infecting virus.

Genome-wide transcriptomic analysis of highly virulent African swine fever virus infection reveals complex and unique virus host interaction.

African swine fever virus (ASFV), one of the most devastating emerging swine pathogens in China, causes nearly 100 % mortality in naive herds. Here, whole-transcriptome RNA-seq analysis was conducted in porcine alveolar macrophages (PAMs) infected with Pig/Heilongjiang/2018 (Pig/HLJ/18) ASFV at different time points. Our data suggested that ASFV genes expression demonstrated a time-depended pattern and ASFV early genes were involved in antagonizing host innate immunity.

Open reading frame 3 protein of hepatitis E virus: Multi-function protein with endless potential.

Hepatitis E virus (HEV), a fecal-orally transmitted foodborne viral pathogen, causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the identification of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. HEV-open reading frame (ORF) 3, the smallest ORF in HEV genomes, initially had been perceived as an unremarkable HEV accessory protein.

A broadly neutralizing monoclonal antibody induces broad protection against heterogeneous PRRSV strains in piglets.

Neutralizing antibodies (NAbs) have attracted attention as tools for achieving PRRSV control and prevention, but viral antigenic variation undermines the abilities of NAbs elicited by attenuated PRRSV vaccines to confer full protection against heterogeneous PRRSV field isolates. As demonstrated in this study, the monoclonal antibody (mAb) mAb-PN9cx3 exhibited broad-spectrum recognition and neutralizing activities against PRRSV-1 and PRRSV-2 strains in vitro. Furthermore, in vivo experiments revealed that the administration of two 10-mg doses of mAb-PN9cx3 before and after the inoculation of piglets with heterologous PRRSV isolates (HP-PRRSV-JXA1 or PRRSV NADC30-like strain HNhx) resulted in significant reduction of the PRRSV-induced pulmonary pathological changes and virus loads in porcine alveolar macrophages (PAMs) compared with the results obtained with mAb-treated isotype controls.

Proteomic Analysis of ISGylation in Immortalized Porcine Alveolar Macrophage Cell Lines Induced by Type I Interferon.

Interferon-stimulated gene product 15 (ISG15), a ubiquitin-like molecule, can be conjugated to protein substrates through a reversible process known as ISGylation. ISG15 and ISGylation are both strongly upregulated by type I interferons and play putative key roles in host innate immunity against viral infection. However, the function of ISGylation and identities of ISGylation substrates are largely unknown.

Structural Characterization of Non-structural Protein 9 Complexed With Specific Nanobody Pinpoints Two Important Residues Involved in Porcine Reproductive and Respiratory Syndrome Virus Replication.

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV), is a widespread viral disease that has led to huge economic losses for the global swine industry. Non-structural protein 9 (Nsp9) of PRRSV possesses essential RNA-dependent RNA polymerase (RdRp) activity for viral RNA replication. Our previous report showed that Nsp9-specific nanobody, Nb6, was able to inhibit PRRSV replication.