Spastin is required for human immunodeficiency virus-1 efficient replication through cooperation with the endosomal sorting complex required for transport (ESCRT) protein

Wenyuan Shen; Chang Liu; Yue Hu; Qian Ding; Jiabin Feng; Zhou Liu; Xiaohong Kong

doi:10.1016/j.virs.2023.05.006

June 2023

Citation: Wenyuan Shen, Chang Liu, Yue Hu, Qian Ding, Jiabin Feng, Zhou Liu, Xiaohong Kong. Spastin is required for human immunodeficiency virus-1 efficient replication through cooperation with the endosomal sorting complex required for transport (ESCRT) protein .VIROLOGICA SINICA, 2023, 38(3) : 448-458. http://dx.doi.org/10.1016/j.virs.2023.05.006

Spastin is required for human immunodeficiency virus-1 efficient replication through cooperation with the endosomal sorting complex required for transport (ESCRT) protein

Wenyuan Shen ^a,b,c ,
Chang Liu ^a ,
Yue Hu ^a,d ,
Qian Ding ^a ,
Jiabin Feng ^a ,
Zhou Liu ^a ,
Xiaohong Kong ^{a
,,}

a. Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin, 300071, China;
b. Department of Spine Surgery, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China;
c. 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;
d. Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, 300192, China

Corresponding author: Xiaohong Kong, kongxh@nankai.edu.cn
Received Date: 02 August 2022
Accepted Date: 08 May 2023
Available online: 11 May 2023

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.
- HIV-1 replication
- , Spastin
- , Gag production
- , Lysosomal degradation
- , Endosomal sorting complex required for transport (ESCRT)

Electronic Supplementary Material

10.1016j.virs.2023.05.006-ESM.docx
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