Equine Mx1 Restricts Influenza A Virus Replication by Targeting at Distinct Site of its Nucleoprotein.
Fatima U, Zhang Z, Zhang H, Wang XF, Xu L, Chu X, Ji S, Wang X.
Viruses. 2019 Dec 2;11(12). pii: E1114. doi: 10.3390/v11121114.
Applications: Stimulation of equine monocyte-derived macrophages in culture
Interferon-mediated host factors myxovirus (Mx) proteins are key features in regulating influenza A virus (IAV) infections. Viral polymerases are essential for viral replication. The Mx1 protein has been known to interact with viral nucleoprotein (NP) and PB2, resulting in the influence of polymerase activity and providing interspecies restriction. The equine influenza virus has evolved as an independent lineage to influenza viruses from other species. We estimated the differences in antiviral activities between human MxA (huMxA) and equine Mx1 (eqMx1) against a broad range of IAV strains. We found that huMxA has antiviral potential against IAV strains from non-human species, whereas eqMx1 could only inhibit the polymerase activity of non-equine species. Here, we demonstrated that NP is the main target of eqMx1. Subsequently, we found adaptive mutations in the NP of strains A/equine/Jilin/1/1989 (H3N8JL89) and A/chicken/Zhejiang/DTID-ZJU01/2013 (H7N9ZJ13) that confer eqMx1 resistance and sensitivity respectively. A substantial reduction in Mx1 resistance was observed for the two mutations G34S and H52N in H3N8JL89 NP. Thus, eqMx1 is an important dynamic force in IAV nucleoprotein evolution. We, therefore, suggest that the amino acids responsible for Mx1 resistance should be regarded as a robust indicator for the pandemic potential of lately evolving IAVs.
The effect of equine herpesvirus type 4 on type-I interferon signaling molecules.
Oladunni FS, Reedy S, Balasuriya UBR, Horohov DW, Chambers TM.
Vet Immunol Immunopathol. 2020 Jan;219:109971. doi: 10.1016/j.vetimm.2019.109971. Epub 2019 Nov 2.
Applications: Confluent EECs treated with equine IFN alpha t stimulate phosphorylation of STAT proteins.
Beyond Gut Instinct: Metabolic Short-Chain Fatty Acids Moderate the Pathogenesis of Alphaherpesviruses.
Poelaert KCK, Van Cleemput J, Laval K, Descamps S, Favoreel HW, Nauwynck HJ.
Front Microbiol. 2019 Apr 5;10:723. doi: 10.3389/fmicb.2019.00723. eCollection 2019.
Applications: Equine IFN alpha proteins was used as a positive control in an anti-viral assay.
Abstract
Short-chain fatty acids (SCFA), such as sodium butyrate (SB), sodium propionate (SPr), and sodium acetate (SAc), are metabolic end-products of the fermentation of dietary fibers. They are linked with multiple beneficial effects on the general mammalian health, based on the sophisticated interplay with the host immune response. Equine herpesvirus 1 (EHV1) is a major pathogen, which primarily replicates in the respiratory epithelium, and disseminates through the body via a cell-associated viremia in leukocytes, even in the presence of neutralizing antibodies. Infected monocytic CD172a+ cells and T-lymphocytes transmit EHV1 to the endothelium of the endometrium or central nervous system (CNS), causing reproductive or neurological disorders. Here, we questioned whether SCFA have a potential role in shaping the pathogenesis of EHV1 during the primary replication in the URT, during the cell-associated viremia, or at the level of the endothelium of the pregnant uterus and/or CNS. First, we demonstrated the expression of SCFA receptors, FFA2 and FFA3, within the epithelium of the equine respiratory tract, at the cell surface of immune cells, and equine endothelium. Subsequently, EHV1 replication was evaluated in the URT, in the presence or absence of SB, SPr, or SAc. In general, we demonstrated that SCFA do not affect the number of viral plaques or virus titer upon primary viral replication. Only SB and SPr were able to reduce the plaque latitudes. Similarly, pretreatment of monocytic CD172a+ cells and T-lymphocytes with different concentrations of SCFA did not alter the number of infected cells. When endothelial cells were treated with SB, SPr, or SAc, prior to the co-cultivation with EHV1-inoculated mononuclear cells, we observed a reduced number of adherent immune cells to the target endothelium. This was associated with a downregulation of endothelial adhesion molecules ICAM-1 and VCAM-1 in the presence of SCFA, which ultimately lead to a significant reduction of the EHV1 endothelial plaques. These results indicate that physiological concentrations of SCFA may affect the pathogenesis of EHV1, mainly at the target endothelium, in favor of the fitness of the horse. Our findings may have significant implications to develop innovative therapies, to prevent the devastating clinical outcome of EHV1 infections.
Equine Tetherin Blocks Retrovirus Release and Its Activity Is Antagonized by Equine Infectious Anemia Virus Envelope Protein.
Yin X, Hu Z, Gu Q, Wu X, Zheng YH, Wei P, Wang X.
J Virol. 2014 Jan;88(2):1259-70. doi: 10.1128/JVI.03148-13. Epub 2013 Nov 13.
Applications: Human embryonic kidney (HEK) 293T cells, equine dermal cells, equine vascular endothelial cells, and HeLa cells were cultured with equine IFN alpha
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