Porcine epidemic diarrhea virus (PEDV) causes devastating enteric disease in piglets, yet the mechanistic basis of antibody-mediated neutralization remains poorly understood. Here, we determined the structure of PEDV HNXX-strain spike domain B (S1B) simultaneously bound by C62, a neutralizing porcine monoclonal antibody against PEDV G2 strains, and N34, a non-neutralizing porcine PEDV antibody. The structure reveals that C62 targets a conserved, cryptic epitope that is accessible only when S1B adopts an “up” conformation. Functionally, we showed that C62 has substantially stronger activity than N34 in triggering S-trimer disassembly and inducing the formation of proteinase K-resistant, post-fusion-like S2 structures. Despite the weaker triggering activity of N34, both C62 and N34 can function as artificial receptors. Notably, although the C62 epitope is conserved across both G1 and G2 strains, C62 exhibits G2-strain-biased neutralizing activity. We further showed that differences in cell-surface membrane fusion activity among PEDV spikes correlate with distinct viral entry pathways and are jointly determined by the S1A and S1B sequences. Together, our findings identify a strain-specific vulnerable site on the PEDV S-trimer and provide insight into how cell-surface membrane fusion activity may influence viral entry pathway selection and antibody neutralization efficacy.
Jian-Bo Liu, Sheng Wang, Zimu Li et al.· bioRxiv· 0 citations
Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen in swine, causing substantial economic losses globally. The host acute-phase response to PRRSV infection and its role in antiviral defense remain poorly understood. In this study, we identify serum amyloid A2 (SAA2) as a key acute-phase protein that is induced during PRRSV infection and demonstrate its potent antiviral activity against this virus. While both SAA2 and SAA3 were upregulated in PRRSV-infected primary porcine alveolar macrophages, functional analyses revealed that SAA2 exerted anti-PRRSV effects. Both the ectopic expression of SAA2 and treatment with recombinant SAA2 protein significantly inhibited PRRSV replication in cultured cells. Mechanistically, SAA2 directly binds to PRRSV particles through interactions with phosphatidylinositol 4,5-bisphosphate (PIP2), a host-derived lipid membrane component in the virus particles, as well as the major envelope glycoprotein GP5. The anti-PRRSV activity of SAA2 was counteracted by high-density lipoprotein (HDL), revealing a physiological regulatory mechanism. Structure-function analysis further identified the N-terminal α-helix (encoded by exon 1) as essential for SAA2-mediated viral inhibition. Our findings unveil a novel antiviral strategy in which a host acute-phase protein directly targets enveloped virions, highlighting SAA2 as a potential target for intervention against PRRSV.
Shuai Li, Yuanxiang Xiong, L. Fang et al.· Antiviral Research· 0 citations
