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

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.

Automated summary

This study found that the replication of human immunodeficiency virus-1 (HIV-1) is inhibited when the level of spastin protein in cells is reduced, because spastin enhances virus production by promoting the lysosomal degradation of the Gag protein. Further investigation revealed that increased sodium tolerance 1 (IST1), a subunit of the endosomal sorting complex required for transport (ESCRT), can interact with the MIT domain of spastin to regulate the production of intracellular Gag. In summary, spastin is crucial for HIV-1 replication, and the interaction between spastin and IST1 facilitates virus production by regulating the intracellular trafficking and degradation of Gag protein. Therefore, spastin may serve as a new target for HIV-1 prophylactic and therapy.