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In this study, we investigated the role of autophagy, primarily using macrophage cell models co-infected with HIV-1 and Mtb. Our findings indicate that HIV-1 infection or latency significantly suppresses autophagy in macrophages, thereby creating a permissive environment for the survival and replication of intracellular Mtb. Co-infection experiments demonstrated that Mtb exacerbates the autophagy suppression induced by HIV-1, further promoting bacterial proliferation. Notably, pharmacological activation of autophagy using berbamine (BBM), a natural compound, significantly reduced HIV-1 latency reactivation and decreased the intracellular Mtb burden. Colocalization of LC3 with the HIV-1 capsid protein p24 and Mtb was observed using a confocal microscope. Mechanistic investigations revealed that BBM-induced autophagy is mediated by elevated levels of cytosolic reactive oxygen species (ROS), which trigger autophagosome formation and lysosomal degradation. However, prolonged ROS elevation poses a risk of cellular damage; thus, BBM concurrently upregulates the antioxidant enzyme glutathione peroxidase 4 (GPX4) to alleviate oxidative stress and maintain redox homeostasis. These findings underscore autophagy as a dual-function mechanism that restricts both viral persistence and bacterial survival during co-infection. This study highlights the therapeutic potential of targeting the crosstalk between autophagy and ROS to manage HIV-1-Mtb co-infection and suggests BBM as a promising candidate for further preclinical evaluation. These insights may inform the development of host-directed therapies aimed at improving clinical outcomes in co-infected patients.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf095","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T19:06:16Z","timestamp":1751137576000},"source":"Crossref","is-referenced-by-count":3,"title":["Berbamine promotes autophagy and GPX4 expression through inducing abundant ROS to restrict HIV-1 and Mtb coinfection in macrophages"],"prefix":"10.1093","volume":"117","author":[{"given":"Xuefeng","family":"Zhou","sequence":"first","affiliation":[{"name":"Graduate School, Guangzhou Medical University , No. 1, Xinzao Road, Xinzao Town, Panyu District, Guangzhou 511436 ,","place":["China"]},{"name":"Guangzhou National Laboratory , No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005 ,","place":["China"]},{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , No. 29, Bulan Road, Longgang District, Shenzhen 518112 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , No. 29, Bulan Road, Longgang District, Shenzhen 518112 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Ou","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , No. 29, Bulan Road, Longgang District, Shenzhen 518112 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Third People's Hospital of Wuzhou , No. 42, Tangyuan Road, Wanxiu District, Wuzhou 543000 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingzhi","family":"Cao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , No. 29, Bulan Road, Longgang District, Shenzhen 518112 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University , No. 1838, Shatai Road, Baiyun District, Guangzhou 510515 ,","place":["P. 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