Biomedical subjects

Haixue Zheng

Publications and source records attributed to Haixue Zheng.

3 recordsLinked to original sources

PubMed2026

Genotype II Live-Attenuated ASFV Vaccine Bearing 24 Genes Deletion in 3 Independent Regions Is Able to Provide Complete Protection Against Homologous Lethal Challenge.

African swine fever (ASF) is an acute, febrile, and highly contagious infectious disease of swine with the etiological agent of African swine fever virus (ASFV). The mortality rate of virulent strains is as high as 100%. Strengthening biosafety is so far the most effective way to prevent and control ASF. Therefore, it is urgent to develop a safe and effective vaccine. In this study, a Genotype II live-attenuated ASF vaccine bearing 24 genes deletion in 3 independent regions was constructed based on the highly virulent Eurasian strain ASFV CN/GS 2018 backbone. The resulting mutant ASFV-Δ24 is characterized by complete deletion of 24 genes distributed in 3 genomic positions of 852 to 11 468, 19 732 to 22 929, and 179 519 to 180 617, among which MGF100 and whole MGF300 families are pioneeringly removed. The ASFV-Δ24 displayed a delayed and reduced replication kinetics as well as aberrant icosahedral empty particles devoid of a nucleoid when compared to the parental virus. Animal experiments showed that ASFV-Δ24 was completely attenuated in animals as evidenced by stable body temperature and no ASF-compatible clinical signs in vaccinated pigs. The ASFV-Δ24 could provide complete homologous protection against lethal challenge, as vaccinated pigs demonstrated boosted antibody response, transient but low levels of viremia in blood and virus titers in organs as well as almost undetectable viral shedding. Gene deletions in multiple regions are helpful for prevention of virulence reversion. These results indicate that ASFV-Δ24 can be used as an effective and promising candidate vaccine to control the spread of ASFV.

Animals↗

PubMed2025

African Swine Fever Virus MGF 360-2L Disrupts Host Antiviral Immunity Based on Transcriptomic Analysis.

Background/Objectives: The African swine fever virus (ASFV) multi-gene family (MGF) 360 proteins play critical roles in immune evasion, replication regulation, and virulence determination. Despite substantial advances in this field, the functional roles of many members within this gene family remain to be fully characterized. Methods: In this study, Transcriptional kinetics analysis indicated that the expression profile of MGF 360-2L was consistent with that of the late marker gene B646L (p72). Transcriptomic profiling identified 13 and 171 differentially expressed genes (DEGs) at 12 and 24 h post-infection (hpi) with ΔMGF 360-2L, respectively. Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these DEGs were predominantly enriched in Type I interferon (IFN-I) signaling pathways. It is noteworthy that transcriptome analysis further demonstrates that the absence of MGF 360-2L specifically results in the dysregulation of expression of the replication-essential genes E199L and E301R. These findings indicate that MG F360-2L is essential for maintaining the stable expression of these proteins. Conclusions:MGF 360-2L is a late gene that contributes to the precise regulation of viral protein expression and modulates the host immune response during infection.

African swine fever virus↗

PubMed2025

Genome-scale CRISPR screen identifies TMEM198 driving double membrane vesicle formation in swine alphacoronavirus and murine betacoronavirus infected cells.

COVID-19 pandemic caused by the SARS-CoV-2 which is well-publicized cross-species transmissibility. SARS-CoV-2 belongs to genus Betacoronavirus, several pathogenic alphacoronaviruses have shown similar patterns of emergence. Much less attention paid to host factors required for alphacoronavirus replication compared to those of betacoronaviruses. Here, we utilized a genome-wide CRISPR-Cas9-based screen to identify TMEM198 as a critical host protein for double-membrane vesicle (DMVs) formation during the replication of swine alphacoronavirus. Gene deletion of TMEM198 led to a reduction in the levels of viral infection in cells, whereas the ectopic expression of TMEM198 correspondingly resulted in an increase in infection levels. At the mechanistic level, TMEM198 directly binds to the C-terminal of nonstructural protein 3 (nsp3c) and nonstructural protein 4 (nsp4) to participate in the formation of DMVs. The first 35 amino acids at the N-terminal of TMEM198 are critical for the formation of DMVs and viral replication. Moreover, mice with a gene deletion of TMEM198 exhibit reduced susceptibility to the Betacoronavirus MHV. These results identify the function of TMEM198 in the formation of DMVs during the replication of swine alphacoronavirus and murine betacoronavirus.

Animals↗