Investigation of SARS-CoV-2 individual proteins reveals the in vitro and in vivo immunogenicity of membrane protein.
Investigation of SARS-CoV-2 individual proteins reveals the in vitro and in vivo immunogenicity of membrane protein.
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DOI：
10.1038/s41598-023-49077-2
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发表时间：
2023-12-18
影响因子：
4.6
通讯作者：
Scarneo, Scott
中科院分区：
文献类型：
--
作者：
Haystead, Timothy;Lee, Eric;Cho, Kirstin;Gullickson, Gail;Hughes, Philip;Krafsur, Greta;Freeze, Robert;Scarneo, Scott
在SARS-CoV-2患者中的证据已经确定，病毒感染伴随着肺系统内免疫细胞和基质细胞炎症介质的表达。然而，个别SARS-CoV-2蛋白的免疫原性尚未得到评估。SARS-CoV-2病毒由29种蛋白质组成，分为非结构蛋白（NSP）、结构蛋白（SP）或辅助蛋白。本研究旨在评估NSP 1、7、8、9、10、12、14、16和SP的刺突蛋白（全长、S1、S2和受体结合域亚基）、核衣壳和膜SARS-CoV-2蛋白对THP-1和人外周血单核细胞（PBMCs）的免疫原性。我们的研究结果表明，各种SARS-CoV-2蛋白可引起促炎免疫反应，其表现为细胞因子TNF、IL-6和IL-1β的增加。我们的研究结果支持SARS-CoV-2膜蛋白诱导THP-1和人PBMC中TNF、IL-6、IL-1β和IL-10表达的显著增加。对雄性和雌性BALB/c小鼠鼻内膜蛋白刺激的进一步评估显示，BALF（支气管肺泡灌洗液）促炎细胞因子表达增加，细胞含量升高，以中性粒细胞为主，并伴有细支气管周围和血管周围淋巴单核细胞和中性粒细胞炎症。我们的研究结果表明，单个膜相关的SARS-CoV-2蛋白诱导了强大的免疫反应，这可能导致中至重度COVID-19患者肺部病毒诱导的细胞因子释放综合征（CRS）。我们假设，免疫功能正常小鼠的SARS-CoV-2膜攻击可以作为开发SARS-CoV-2诱导的肺部炎症的新疗法的充分替代，从而避免在BSL-3条件下进行昂贵的活病毒研究。
Evidence in SARS-CoV-2 patients have identified that viral infection is accompanied by the expression of inflammatory mediators by both immune and stromal cells within the pulmonary system. However, the immunogenicity of individual SARS-CoV-2 proteins has yet to be evaluated. The SARS-CoV-2 virus consists of 29 proteins, categorized either as nonstructural proteins (NSP’s), structural proteins (SP’s) or accessory proteins. Here we sought to evaluate the immunogenicity of NSP 1, 7, 8, 9, 10, 12, 14, 16 and the SP’s spike protein (full length, S1, S2 and receptor binding domain subunits), nucleocapsid and membrane SARS-CoV-2 proteins against THP-1 and human peripheral blood mononuclear cells (PBMCs). Our results indicate that various SARS-CoV-2 proteins elicit a proinflammatory immune response indicated by increases in cytokines TNF, IL-6 and IL-1β. Our results support that SARS-CoV-2 membrane protein induced a robust increase of TNF, IL-6, IL-1β and IL-10 expression in both THP-1 and human PBMC’s. Further evaluation of intranasal membrane protein challenge in male and female BALB/c mice show increases in BALF (bronchalveolar lavage fluid) proinflammatory cytokine expression, elevated cellularity, predominantly neutrophilic, and concomitant peribronchiolar and perivascular lymphomononuclear and neutrophilic inflammation. Our results suggest that individual membrane associated SARS-CoV-2 proteins induce a robust immune response that may contribute to viral induced cytokine release syndrome (CRS) in the lungs of moderate to severe COVID-19 patients. We posit that SARS-CoV-2 membrane challenges in immune-competent mice can serve as an adequate surrogate for the development of novel treatments for SARS-CoV-2 induced pulmonary inflammation, thereby avoiding expensive live virus studies under BSL-3 conditions.
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影响因子：
2.2
作者：
Soriano, Vicente;de-Mendoza, Carmen;Edagwa, Benson;Trevino, Ana;Barreiro, Pablo;Fernandez-Montero, Jose, V;Gendelman, Howard E.
通讯作者：
Gendelman, Howard E.
影响因子：
6.4
作者：
Amjadi, Maya F.;Adyniec, Ryan R.;Shelef, Miriam A.
通讯作者：
Shelef, Miriam A.
影响因子：
45.3
作者：
Loprinzi, Charles L.;Lacchetti, Christina;Hershman, Dawn L.
通讯作者：
Hershman, Dawn L.
COVID-19 治疗和发病机制，包括 K18-hACE2 小鼠的嗅觉丧失。
影响因子：
64.8
作者：
Zheng J;Wong LR;Li K;Verma AK;Ortiz ME;Wohlford-Lenane C;Leidinger MR;Knudson CM;Meyerholz DK;McCray PB Jr;Perlman S
通讯作者：
Perlman S
影响因子：
6.7
作者：
Rawle DJ;Le TT;Dumenil T;Yan K;Tang B;Nguyen W;Watterson D;Modhiran N;Hobson-Peters J;Bishop C;Suhrbier A
通讯作者：
Suhrbier A