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Updated: Jul 30, 2025

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
Spastin is required for human immunodeficiency virus-1 efficient replication through cooperation with the endosomal
Wenyuan Shen1, Chang Liu2, Yue Hu3
1Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China; Department of Spine Surgery, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Abstract:
Human immunodeficiency virus-1 (HIV-1) encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction. Spastin, a microtubule severing protein, is an identified HIV-1 dependency factor, but the mechanism regulating HIV-1 is unclear. Here, the study showed that knockdown of spastin inhibited the production of the intracellular HIV-1 Gag protein and new virions through enhancing Gag lysosomal degradation. Further investigation showed that increased sodium tolerance 1 (IST1), the subunit of endosomal sorting complex required for transport (ESCRT), could interact with the MIT domain of spastin to regulate the intracellular Gag production. In summary, spastin is required for HIV-1 replication, while spastin-IST1 interaction facilitates virus production by regulating HIV-1 Gag intracellular trafficking and degradation. Spastin may serve as new target for HIV-1 prophylactic and therapy.
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