Deletion of the African swine fever virus E120R gene completely attenuates its virulence by enhancing host innate immunity and impairing virus release.
Boli Ma, Yiqian Jiang, Nan Li, Fengjie Wang, Qian Li, Huixian Yue, Yanyan Zhang, Rongliang Hu, Faming Miao
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Abstract
African swine fever virus (ASFV) causes a lethal haemorrhagic disease in domestic pigs and poses a major threat to the global swine industry. Currently, no effective commercial vaccines or antiviral drugs are available for ASF control. In this study, we constructed a recombinant E120R gene-deleted virus, ASFV-ΔE120R, based on the highly virulent genotype II strain SY18, to investigate the role of the E120R gene. ASFV-ΔE120R exhibited impaired virion release and formed aberrant tubular structures, rendering viral particles more susceptible to neutralization by convalescent pig sera. ASFV-ΔE120R induced higher levels of transcription of Cytokines, chemokines, and interferon-regulated genes in porcine alveolar macrophages compared with ASFV-WT. In vivo safety evaluation demonstrated that piglets immunized with 5 × 10⁶ TCID₅₀ of ASFV-ΔE120R exhibited no clinical signs or viral nucleic acid in tissues at necropsy on days 4, 7, 10, and 14 post-immunization. Two immunizations at the same dose, 21 days apart, also induced no clinical signs or viral shedding during a 28-day observation. Immunogenicity analysis showed that ASFV-ΔE120R elicited p54-specific antibodies and IFN-γ-secreting PBMC responses. Upon challenge with parental ASFV SY18, two of five pigs (40%) survived, showing elevated antibody levels, IFN-γ-secreting PBMCs, and increased CD8+ IFN-γ+ T cells. Moreover, Cytokines and interferon-stimulated genes were significantly upregulated in survivors. In summary, ASFV-ΔE120R is fully attenuated, safe, and induces both humoral and cellular immune responses, highlighting pE120R as a rational target for ASF vaccine development.
期刊介绍：
Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses.
The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries.
This journal addresses topics of critical biological and clinical importance, including but not limited to:
- Epidemic surveillance
- Clinical manifestations
- Diagnosis and management
- Cellular and molecular pathogenesis
- Innate and acquired immune responses between emerging microbes and their hosts
- Drug discovery
- Vaccine development research
Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.
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