In the heart of Chengdu, China, a team of researchers led by Jialiang Xin from the Key Laboratory of Animal Disease and Human Health of Sichuan Province at Sichuan Agricultural University has made a significant stride in understanding the Goatpox virus (GTPV). Their work, published in the journal *Frontiers in Veterinary Science* (translated as “Veterinary Science Frontiers”), focuses on the N1L gene, a known virulence factor in poxviruses, and its role in GTPV.
The N1L gene has been a subject of interest due to its influence on viral virulence. However, its specific role in GTPV has remained a mystery until now. Xin and his team constructed three recombinant vaccinia virus Tiantan strains (rVVT) to investigate the function of the GTPV N1L gene (gN1L). These strains included rVVT-ΔvN1L (with the N1L gene deleted), rVVT-vN1Lr (with an inserted enhanced green fluorescent protein), and rVVT-gN1L (with the gN1L gene substituted).
The team’s bioinformatics analysis revealed that the gN1L-encoded protein shares a modest homology with the vaccinia virus N1L (vN1L)-encoded protein, suggesting a unique role for gN1L. “The structural stability of the gN1 protein, in contrast to the instability of the vN1 protein, was a striking finding,” noted Xin. This stability could potentially influence the virus’s behavior and pathogenicity.
Growth curve assays showed that gN1L significantly enhances vaccinia virus replication in various cell types, including BHK-21, HeLa, and PK-15 cells. RNA sequencing analysis suggested that this enhancement might be mediated through the PI3K/AKT signaling pathway, a crucial pathway involved in cell growth and survival.
The team also conducted in vitro and in vivo virulence assays, which indicated that gN1L increases viral virulence by up to 133-fold, a 7.5-fold greater effect compared to vN1L. “This substantial increase in virulence underscores the importance of gN1L in the pathogenicity of GTPV,” explained Xin.
Furthermore, viral load measurements in host tissues revealed that gN1L facilitates the virus’s ability to traverse the blood-brain barrier by enhancing its ability to infect glial and endothelial cells. This finding has significant implications for understanding how GTPV spreads and causes disease in goats.
The research conducted by Xin and his team provides novel insights into the functional role of gN1L and offers valuable implications for the development of safer attenuated vaccines against GTPV. “Understanding the role of gN1L is a crucial step towards developing effective control measures for goatpox,” Xin stated.
This study not only advances our understanding of GTPV but also paves the way for future developments in veterinary medicine. The findings could potentially lead to the development of more effective vaccines and treatments, ultimately benefiting the agricultural industry and global food security. As the world continues to grapple with emerging infectious diseases, research like this is more important than ever.