African swine fever (ASF) is a highly contagious and fatal disease caused by the African swine fever virus. Recently, the multigene family and CD2v gene-deleted ASF vaccine candidate HLJ/18-7GD was found to be safe and effective in laboratory and clinical trials. However, the immune-protective mechanisms underlying the effects of HLJ/18-7GD remain unclear. We assessed samples from pigs immunized with a single dose of 10⁶ TCID₅₀ HLJ/18-7GD. We found that pigs immunized with HLJ/18-7GD showed high levels of specific antibodies. T lymphocyte subsets (helper T cells (Th); cytotoxic T lymphocytes (CTL); double-positive T cells (DP-T cells)) were temporarily increased in peripheral blood mononuclear cells (PBMCs) after HLJ/18-7GD immunization. Once the HLJ/18-7GD-immunized pigs had been challenged with virulent HLJ/18, the percentage of Th, CTL, and DP-T cells increased significantly. PBMCs extracted from the pigs induced higher levels of CD8⁺ T cells after infection with the HLJ/18 strain in vitro. The levels of GM-CSF, IFN-γ, and TNF-α were upregulated at 7 days post-inoculation; this finding was contrary to the results obtained after HLJ/18 or HLJ/18ΔCD2v infection. The immune protection from HLJ/18-7GD resulted from many synergies, which could provide a theoretical basis for HLJ/18-7GD as a safe and effective ASF vaccine.

Getah virus (GETV) is a member of the alphavirus genus, and it infects a variety of animal species, including horses, pigs, cattle, and foxes. Human infection with this virus has also been reported. The structure of GETV has not yet been determined. In this study, we report the cryo-EM structure of GETV at a resolution of 3.5 Å. This structure reveals conformational polymorphism of the envelope glycoproteins E1 and E2 at icosahedral 3-fold and quasi-3-fold axes, which is believed to be a necessary organization in forming a curvature surface of virions. In our density map, three extra densities are identified, one of which is believed a “pocket factor”; the other two are located by domain D of E2, and they may maintain the stability of E1/E2 heterodimers. We also identify three N-glycosylations at E1 N141, E2 N200, and E2 N262, which might be associated with receptor binding and membrane fusion. The resolving of the structure of GETV provides new insights into the structure and assembly of alphaviruses and lays a basis for studying the differences of biology and pathogenicity between arthritogenic and encephalitic alphaviruses.

Picornaviruses, as a large family of human and animal pathogens, cause a bewildering array of disease syndromes. Many host factors are implicated in the pathogenesis of these viruses, and some proteins interact with the viral IRES elements to affect function. Here, we report for the first time that cellular hnRNP L specifically interacts with the IRES of the picornavirus FMDV and negatively regulates FMDV replication through inhibiting viral RNA synthesis. Further, our results showed that hnRNP L coimmunoprecipitates with FMDV 3D ^pol in a viral RNA-dependent manner, suggesting that it may remain in the replication complex to function. The data presented here would facilitate further understanding of virus-host interactions and the pathogenesis of picornavirus infections.

The very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) serve as entry receptors for the Semliki Forest virus (SFV). VLDLR interacts with the SFV E1 domain III (DIII) through multiple LDLR class A (LA) domains. However, the ApoER2-mediated SFV entry mechanism remains unclear. Here, we perform biochemical and cellular results and determine the cryogenic electron microscopy (cryo-EM) structures of SFV complexed with ApoER2 LA5 and full-length ApoER2, demonstrating that among the seven LA domains of ApoER2 isoform 1, only LA5 specifically binds to the SFV E1-DIII via a limited interface (353 Ų) and facilitates cell attachment and entry. Site-directed mutagenesis confirms the significance of the residues at the SFV-ApoER2 interface. Significantly, a soluble LA5 decoy receptor neutralizes SFV infection and protects mice from lethal SFV challenge. These findings reveal a LA5-dependent receptor engagement mechanism for SFV entry via ApoER2, distinct from VLDLR.

Senecavirus A (SVA), an emerging causative agent of porcine vesicular disease, belongs to the genus Senecavirus of the family Picornaviridae. The virus has been circulating in pig herds in the USA dating back to 1988, evolved into clinically significant pathogenic SVA variants causing a pandemic in the USA and Canada since 2014, and thereafter gradually spread to the Americas and Asia. To date, most studies have illustrated the infection dynamics, epidemiology, diagnostic methods, and vaccine development, yet the molecular pathogenesis of SVA remains incompletely characterized. As a novel picornavirus capable of establishing persistent subclinical infections, SVA has been detected in tissues such as tonsils and testicles for up to 156 days post-infection, posing a substantial challenge to swine health and production systems. In parallel, SVA has gained attention as an oncolytic virotherapy candidate for neuroendocrine tumors due to its tumor-selective tropism. Therefore, elucidating the mechanisms underlying SVA pathogenesis will not only support the development of effective countermeasures for swine but also inform the engineering of recombinant variants with enhanced therapeutic potential for human oncology. This review comprehensively summarizes the current knowledge on viral and host determinants of SVA pathogenesis, from the viral genome, evolution, and recombination to ANTXR1 host immunity, and programmed cell death, and presents future research directions, aiming to identify key knowledge gaps to guide future studies on SVA.