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一种表达生物发光以评估病毒感染和确定治疗干预措施的人H5N1流感病毒。

A human H5N1 influenza virus expressing bioluminescence for evaluating viral infection and identifying therapeutic interventions.

作者信息

Barre Ramya S, Escobedo Ruby A, Castro Esteban M, Gazi Michal, Castro Joshua D, Cupic Anastasija, Bayoumi Mahmoud, Jackson Nathaniel, Ye Chengin, Nogales Aitor, Platt Roy N, Carrion Ricardo, Anderson Timothy J C, García-Sastre Adolfo, Mostafa Ahmed, Martinez-Sobrido Luis

机构信息

Texas Biomedical Research Institute, San Antonio, TX, USA.

Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA.

出版信息

iScience. 2025 Aug 21;28(9):113402. doi: 10.1016/j.isci.2025.113402. eCollection 2025 Sep 19.

DOI:10.1016/j.isci.2025.113402
PMID:40978136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12446200/
Abstract

A multistate outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 in the United States dairy cattle was first reported on March 2024, followed by a zoonotic cattle-to-human virus transmission to a dairy farm worker in Texas. To facilitate real-time tracking of HPAIV H5N1, we generated a recombinant nanoluciferase (Nluc)-expressing H5N1 virus, HPhTX NSs-Nluc, by introducing an Nluc reporter into the non-structural gene of human A/Texas/37/2024 H5N1 (HPhTX). HPhTX NSs-Nluc replicated with kinetics and plaque morphology comparable to wild-type virus . and , HPhTX NSs-Nluc allowed tracking viral infection in the living animals and their necropsied organs using imaging systems (IVISs). Treatment with baloxavir effectively inhibited HPhTX NSs-Nluc replication, comparable to wild-type virus, validating its applicability for high-throughput screening of potential antiviral therapeutics. These results demonstrate that HPhTX NSs-Nluc is a robust tool for studying H5N1 pathogenesis and assessing antiviral efficacy against HPAIV H5N1.

摘要

2024年3月首次报道了美国奶牛中高致病性禽流感病毒（HPAIV）H5N1的多州疫情爆发，随后出现了从牛到人的人畜共患病毒传播，一名得克萨斯州的奶牛场工人被感染。为便于实时追踪HPAIV H5N1，我们通过将纳米荧光素酶（Nluc）报告基因导入人源A/得克萨斯/37/2024 H5N1（HPhTX）的非结构基因中，构建了表达重组Nluc的H5N1病毒HPhTX NSs-Nluc。HPhTX NSs-Nluc的复制动力学和蚀斑形态与野生型病毒相当。此外，HPhTX NSs-Nluc可利用体内成像系统（IVIS）追踪活体动物及其尸检器官中的病毒感染情况。巴洛沙韦治疗可有效抑制HPhTX NSs-Nluc的复制，与野生型病毒效果相当，证实了其在高通量筛选潜在抗病毒疗法方面的适用性。这些结果表明，HPhTX NSs-Nluc是研究H5N1发病机制和评估抗HPAIV H5N1抗病毒疗效的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/c660c56ccf40/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/d71dd805f6b3/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/06b22e1b3104/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/5af364e0a31c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/3bbdbbb3f240/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/8801cd37fab3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/bb8a8e146b0d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/18113822c2d0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/4cddf895a64a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/de86382081b0/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/b824f1713fe3/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/c660c56ccf40/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/d71dd805f6b3/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/06b22e1b3104/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/5af364e0a31c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/3bbdbbb3f240/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/8801cd37fab3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/bb8a8e146b0d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/18113822c2d0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/4cddf895a64a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/de86382081b0/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/b824f1713fe3/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eda/12446200/c660c56ccf40/gr10.jpg

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