Abstract
BackgroundThe genome of human immunodeficiency virus type 1 (HIV-1) is encapsulated in a core consisting of viral capsid proteins (CA). After viral entry, the HIV-1 core dissociates and releases the viral genome into the target cell, this process is called uncoating. Uncoating of HIV-1 core is one of the critical events in viral replication and several studies show that host proteins positively or negatively regulate this process by interacting directly with the HIV-1 CA.ResultsHere, we show that arginyl-tRNA-protein transferase 1 (ATE1) plays an important role in the uncoating process by governing the optimal core stability. Yeast two-hybrid screening of a human cDNA library identified ATE1 as an HIV-1-CA-interacting protein and direct interaction of ATE1 with Pr55gag and p160gag − pol via HIV-1 CA was observed by cell-based pull-down assay. ATE1 knockdown in HIV-1 producer cells resulted in the production of less infectious viruses, which have normal amounts of the early products of the reverse transcription reaction but reduced amounts of the late products of the reverse transcription. Interestingly, ATE1 overexpression in HIV-1 producer cells also resulted in the production of poor infectious viruses. Cell-based fate-of-capsid assay, a commonly used method for evaluating uncoating by measuring core stability, showed that the amounts of pelletable cores in cells infected with the virus produced from ATE1-knockdown cells increased compared with those detected in the cells infected with the control virus. In contrast, the amounts of pelletable cores in cells infected with the virus produced from ATE1-overexpressing cells decreased compared with those detected in the cells infected with the control virus.ConclusionsThese results indicate that ATE1 expression levels in HIV-1 producer cells contribute to the adequate formation of a stable HIV-1 core. These findings provide insights into a novel mechanism of HIV-1 uncoating and revealed ATE1 as a new host factor regulating HIV-1 replication.Graphic abstract
Highlights
The genome of human immunodeficiency virus type 1 (HIV-1) is encapsulated in a core consisting of viral capsid proteins (CA)
arginyl-tRNA-protein transferase 1 (ATE1) was identified as a protein that interacts with CA region of viral precursor proteins We performed yeast two-hybrid (Y2H) screening to identify host factors that contribute to HIV-1 uncoating
The assay showed that HIV-1 P r55gag and the CA N-terminal domain (CANTD) interacted with ATE1, suggesting that the N-terminal domain of the CA was responsible for interaction with ATE1
Summary
The genome of human immunodeficiency virus type 1 (HIV-1) is encapsulated in a core consisting of viral capsid proteins (CA). The HIV-1 core dissociates and releases the viral genome into the target cell, this process is called uncoating. In complete HIV-1 replication, assembled CA should disassemble at Kishimoto et al Retrovirology (2021) 18:30 viral target cells to release the viral genome. It has been reported that the viral core uncoats in the nucleus, and the importance of proteins involved in core translocation, such as Nup153 and CPSF6, has been confirmed [15, 16] These findings indicate that the stability of the HIV-1 core has an enormous impact on viral replication and host proteins can modulate the stability of the HIV-1 core. Sufficient characterization of CA-interacting proteins is required for resolving uncoating machinery
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