Lei Na

Veterinary infectious diseases impose massive economic losses to global livestock, aquaculture and companion animal industries, while continuously raising zoonotic spillover risks to human populations [1]. Conventional disease control strategies centered on antibiotics and universal vaccination face growing limitations: widespread antimicrobial resistance, incomplete cross-protection of traditional vaccines, and emerging/re-emerging pathogens with evolved immune escape mechanisms collectively demand paradigm shifts in disease intervention [2]. Deciphering molecular host-pathogen crosstalk represents the core breakthrough point to resolve these bottlenecks, as it uncovers how pathogens manipulate host transcriptional programs, Beyond pathogen intrinsic virulence mechanisms, this Research Topic also delivers translational functional research for eco-friendly immunoregulatory feed additives against aquatic bacterial diseases. A probiotic fermented herbal preparation using Bacillus amyloliquefaciens was optimized via single-factor fermentation parameter screening; in largemouth bass feeding and Nocardia seriolae challenge trials, the composite additive significantly elevated growth performance, serum antioxidant enzyme activity, systemic immune gene expression and intestinal microbial diversity, while achieving 77% relative survival post-infection and complete clearance of granulomatous lesions in vital organs [7]. It establishes a sustainable antibiotic substitute for aquaculture disease prevention via dual immunostimulation and gut microecology remodeling.Collectively, all included manuscripts converge on the core logic: dissecting molecular host-pathogen interactions enables rational design of immunomodulatory therapeutics, replacing outdated pathogen-centric control modes. Current contributions lay solid groundwork, yet multiple critical gaps remain unaddressed, including parasitic/fungal pathogen crosstalk, primary host cell models (e.g., porcine alveolar macrophages) verification of cell line-derived discoveries, and large-animal translational validation of candidate vaccines/therapeutics. We anticipate follow-up research expanding this Research Topic's coverage, further bridging molecular pathogenesis and field disease prevention, and supporting One Health-oriented control of veterinary infectious diseases.

African horse sickness (AHS) is a lethal vector-borne disease caused by African horse sickness virus (AHSV) and represents a major threat to equine health and the horse industry. In 2020, outbreaks of AHS caused by AHSV serotype 1 (AHSV-1) were reported in Thailand, increasing the risk of AHS introduction into China. Given the safety issues associated with currently available live attenuated AHS vaccines, the development of safer and more effective vaccination strategies is urgently needed. In this study, we constructed a recombinant fowlpox virus (rFPV) expressing the AHSV-1 VP2 protein as a candidate vaccine, designated rFPV-VP2. The recombinant virus was verified by PCR and Western blot analysis, which confirmed the successful expression of VP2. Preliminary immunization trials were conducted in both mice and horses, and immune responses were evaluated via an indirect enzyme-linked immunosorbent assay (iELISA) and immunofluorescence assay (IFA). The results revealed that VP2-specific antibodies were successfully induced in the serum of rFPV-VP2-immunized animals. Notably, serum from immunized horses showed specific reactivity with AHSV-1, confirming the induction of AHSV-1-specific immune responses. Therefore, these results demonstrate that rFPV-VP2 is a promising candidate vaccine for AHSV-1 and provide a scientific basis for the development of safer preventive strategies.

Equine infectious anemia virus (EIAV) is an important model for the study of pathogenesis in lentiviruses. Studies of viral genome organization and replication mechanisms are fundamental to the understanding of virus pathogenicity. In this study, we identified an unique transcript from EIAV in vivo and in vitro by Sanger sequencing and Northern blotting. The transcript contains a complete open reading frame and has length 369 nt. We named the protein encoded by this transcript S4 and demonstrated its expression in EIAV-infected cells. An S4-deficient EIAV infectious clone displayed obviously impaired virion release and attenuated virus replication in vitro, demonstrating that S4 plays a role in the release step of EIAV. The host restriction factor tetherin has broad-spectrum antiviral activity and prevents the release of a wide range of enveloped viruses, including lentiviruses. Here, we demonstrated that S4 enhances the release of the EIAV-like particle by counteracting the equine tetherin (eqTHN). S4 interacts with the eqTHN and sequesters it within intracellular membrane compartments, attenuating eqTHN expression on the cell surface and thereby disrupting its antiviral activity. Further investigation revealed that S4 retains eqTHN in the endoplasmic reticulum and trans-Golgi network through impacting its anterograde transport to the cell surface and may interfere with the posttranslational modification of this membrane protein. Collectively, our findings uncover an accessory protein, S4, of EIAV and reveal its ability to promote virion release by antagonizing the antiviral activity of the host restriction factor tetherin.

African horse sickness (AHS) is an acute, fatal, contagious disease of animals of the family Equidae and is caused by infection with the African horse sickness virus (AHSV). Based on the outer capsid protein VP2, AHSV is classified into nine serotypes (AHSV−1 to −9) with little or no serological cross-reactivity between them. In 2020, AHS outbreaks caused by AHSV−1 were reported in Thailand and Malaysia, marking the first occurrences of AHS in Southeast Asia. However, little is known about the antigenic profile of AHSV−1 VP2. In this study, a recombinant VP2 protein was expressed in Escherichia coli and used as an immunogen, and three monoclonal antibodies (mAbs), designated 7D11, 10A9, and 9E7, against AHSV−1 VP2, were generated. These three mAbs were then successfully used in IFA, WB, and ELISA for the detection of AHSV−1 VP2. Two overlapping linear epitopes, ⁶⁷⁰NEFDFE⁶⁷⁵ (E670–675) recognized by 9E7 and ⁶⁷⁰NEFDF⁶⁷⁴ (E670–674) recognized by 7D11 and 10A9, were identified through truncation of GST-fused VP2. Amino acid sequence alignment shows that the ⁶⁷⁰NEFDFE⁶⁷⁵ motif is completely conserved within AHSV−1 but is highly divergent in other AHSV serotypes. Our studies provide an important tool for basic research into AHSV−1 and for the diagnosis of AHSV−1.

Species-specific differences in acidic nuclear phosphoprotein 32 family member A (ANP32A) determine the restriction of avian-signature polymerase in mammalian cells. Mutations that evade this restriction, such as PB2-E627K, are frequently acquired when avian influenza A viruses jump from avian hosts to mammalian hosts. However, the mechanism underlying this adaptation process is still unclear. Here, we report that host factor ANP32 proteins can be incorporated into influenza viral particles through combination with the viral RNA polymerase (vPol) and then transferred into targeted cells where they support virus replication. The packaging of the ANP32 proteins into influenza viruses is dependent on their affinity with the vPol. Avian ANP32A (avANP32A) delivered by avian influenza A virions primes early viral replication in mammalian cells, thereby favoring the downstream interspecies transmission event by increasing the total amount of virus carrying adaptive mutations. Our study clarifies one role of avANP32A where it is used by avian influenza virus to help counteract the restriction barrier in mammals.

Recently, an increasing number of studies have shown that long noncoding RNAs (lncRNAs) are involved in host metabolism after infection with pseudorabies virus (PRV). In our study, via RNA sequencing analysis, a total of 418 mRNAs, 137 annotated lncRNAs, and 312 new lncRNAs were found to be differentially expressed. These lncRNAs were closely associated with metabolic regulation and immunity-related signalling pathways, including the T-cell receptor signalling pathway, chemokine signalling pathway, mitogen-activated protein kinase (MAPK) signalling pathway, TNF signalling pathway, Ras signalling pathway, calcium signalling pathway, and phosphatidylinositol signalling system. Real-time PCR indicated that several mRNAs and lncRNAs involved in the regulation of the immune effector process, T-cell receptor signalling pathway, TNF signalling pathway, MAPK signalling pathway, and chemokine signalling pathways were significantly expressed. These mRNAs and lncRNAs might play a role in PRV infection.

Species differences in the host factor ANP32A/B result in the restriction of avian influenza virus polymerase (vPol) in mammalian cells. Efficient replication of avian influenza viruses in mammalian cells often requires adaptive mutations, such as PB2-E627K, to enable the virus to use mammalian ANP32A/B. However, the molecular basis for the productive replication of avian influenza viruses without prior adaptation in mammals remains poorly understood. We show that avian influenza virus NS2 protein help to overcome mammalian ANP32A/B-mediated restriction to avian vPol activity by promoting avian vRNP assembly and enhancing mammalian ANP32A/B-vRNP interactions. A conserved SUMO-interacting motif (SIM) in NS2 is required for its avian polymerase-enhancing properties. We also demonstrate that disrupting SIM integrity in NS2 impairs avian influenza virus replication and pathogenicity in mammalian hosts, but not in avian hosts. Our results identify NS2 as a cofactor in the adaptation process of avian influenza virus to mammals.

Equine infectious anemia virus (EIAV) is a member of the Lentivirus genus in the Retroviridae family that exhibits a genomic structure similar to that of HIV-1. The S2 accessory proteins play important roles in viral replication in vivo and in viral pathogenicity; however, studies on S2 evolution in vivo are limited. This study analyzed the evolutionary characteristics of the S2 gene of a pathogenic EIAV strain, EIAV_LN40, in four experimentally infected horses. The results demonstrated that 14.7% (10 of 68 residues) of the stable amino acid mutations occurred longitudinally in S2 during a 150-day infection period. Further analysis revealed that six of the ten mutated residues were positively selected during the infection. Alignment and phylogenetic analyses showed that the S2 gene sequences of viruses isolated from the infected horses at the early stage of EIAV_LN40 infection were highly homologous and similar to the vaccine-specific sequence. The S2 gene variants isolated from the febrile episodes and late phase of infection became homologous to the S2 gene sequence of the inoculating EIAV_LN40 strain. Our results indicate that the S2 gene evolves in diversity and divergence in vivo in different stages of EIAV infection and that this evolution correlates with the pathogenicity of the virus.