Robinson-McCarthy Lindsey R, Zirckel Kylie E, Simmons Holly C, Le Sage Valerie, McCarthy Kevin R
Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
bioRxiv. 2025 Feb 27:2025.02.27.640582. doi: 10.1101/2025.02.27.640582.
A panzootic of highly pathogenic avian influenza (HPAI) H5N1 viruses from clade 2.3.4.4b has triggered a multistate outbreak in United States dairy cattle and an unknown number of human infections. HPAI viruses are handled in specialized biocontainment facilities. Ethical considerations limit certain experimental evolution experiments aimed at assessing viral resistance to potential therapeutics. We have developed a replicating recombinant vesicular stomatitis virus (rVSV) where we replaced its glycoprotein with the hemagglutinin (HA) and neuraminidase (NA) genes of a 2.3.4.4b H5N1 virus (rVSV-H5N1dc2024), which is free of these constraints. This virus grows to high titers and encodes a fluorescent reporter to track infection. We demonstrate the utility of rVSV-H5N1dc2024 in neutralization experiments, evaluating antibody escape and characterization of resistance mutations to NA inhibitors. rVSV-H5N1dc2024 or similar viruses may accelerate efforts to develop and evaluate interventions against this emerging threat to human and animal health.
来自2.3.4.4b分支的高致病性禽流感（HPAI）H5N1病毒的一次动物大流行引发了美国奶牛的多州疫情以及数量不明的人类感染。HPAI病毒在专门的生物安全设施中处理。伦理考量限制了某些旨在评估病毒对潜在治疗药物耐药性的实验进化实验。我们开发了一种复制性重组水疱性口炎病毒（rVSV），我们用2.3.4.4b H5N1病毒的血凝素（HA）和神经氨酸酶（NA）基因取代了其糖蛋白（rVSV-H5N1dc2024），该病毒不受这些限制。这种病毒能生长到高滴度，并编码一种荧光报告基因来追踪感染。我们展示了rVSV-H5N1dc2024在中和实验中的效用，评估抗体逃逸以及对NA抑制剂耐药突变的特征。rVSV-H5N1dc2024或类似病毒可能会加速开发和评估针对这种对人类和动物健康的新出现威胁的干预措施的努力。
