da Silva Menegatto Marília Bueno, Ferraz Ariane Coelho, Lima Rafaela Lameira Souza, Guimarães Pedro Henrique, Ola-Olu Oluwashola Samuel, Machado-Junior Pedro Alves, Carvalho Malta Wellington, de Fátima Silva Moraes Thaís, Silva Bezerra Frank, de Mello Silva Breno, de Magalhães José Carlos, Dos Reis Jordana Grazziela Alves Coelho, da Fonseca Flávio Guimarães, de Souza Trindade Giliane, Geessien Kroon Erna, de Brito Magalhães Cintia Lopes
Programa de Pós Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Programa de Pós Graduação em Biotecnologia, Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Sci Rep. 2025 Aug 13;15(1):29771. doi: 10.1038/s41598-025-14433-x.
The vaccinia virus (VACV) is the most studied and well-characterised member of the Poxviridae family. However, the mechanisms through which it modulates redox homeostasis in host cells remain unclear. Although oxidative stress, which is marked by elevated levels of reactive species, contributes to the pathogenesis of many viral infections, poxviruses may adopt distinct strategies. VACV has redox effector proteins that are released into the cytosol when the virus penetrates the host cell. This study demonstrates for the first time that VACV infection leads to the activation of the nuclear factor erythroid 2 (Nrf2)/antioxidant response element pathway, a key regulator of cellular antioxidant responses, a mechanism not previously described for any poxvirus. Using BSC-40 cells, we observed that VACV significantly reduced reactive oxygen and nitrogen species levels, downregulated inducible nitric oxide synthase, and enhanced the activity of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. This antioxidant shift is correlated with increased Nrf2 activity and the upregulation of its downstream targets. This virus-induced antioxidant state may be an immunomodulatory mechanism that facilitates viral replication by dampening host defence. Thus, our findings expand the current understanding of virus-host interactions in poxvirus infections.
痘苗病毒（VACV）是痘病毒科中研究最多、特征最明确的成员。然而，其调节宿主细胞氧化还原稳态的机制仍不清楚。尽管以活性物质水平升高为特征的氧化应激会导致许多病毒感染的发病机制，但痘病毒可能采取不同的策略。VACV具有氧化还原效应蛋白，当病毒穿透宿主细胞时，这些蛋白会释放到细胞质中。本研究首次证明，VACV感染会导致核因子红细胞2（Nrf2）/抗氧化反应元件途径的激活，这是细胞抗氧化反应的关键调节因子，此前尚未有任何痘病毒描述过这种机制。使用BSC - 40细胞，我们观察到VACV显著降低了活性氧和氮物质水平，下调了诱导型一氧化氮合酶，并增强了超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶等抗氧化酶的活性。这种抗氧化转变与Nrf2活性增加及其下游靶点的上调相关。这种病毒诱导的抗氧化状态可能是一种免疫调节机制，通过抑制宿主防御来促进病毒复制。因此，我们的发现扩展了目前对痘病毒感染中病毒 - 宿主相互作用的理解。
