Sec24C is an HIV-1 host dependency factor crucial for virus replication

Rebensburg, Stephanie V; Wei, Guochao; Larue, Ross C.; Lindenberger, Jared; Francis, Ashwanth C.; Annamalai, Arun S.; Morrison, James H.; Shkriabai, Nikoloz; Huang, Szu-Wei; KewalRamani, Vineet N.; Poeschla, Eric M.; Melikyan, Gregory B.; Kvaratskhelia, Mamuka

doi:10.1038/s41564-021-00868-1

Cited by 64 publications

(72 citation statements)

References 71 publications

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“…CPSF6 binds to a preformed pocket generated by the NTD-CTD interface with a higher affinity to a multimerized form of CA than CA monomers [ 187 – 189 ]. Interestingly, HIV-1 uses this binding pocket to interact with other proteins, such as NUP153 and Sec24C [ 95 , 188 – 190 ]. Amino acid substitutions in this CPSF6-binding pocket alter a wide variety of phenotypic properties of HIV-1 and are instrumental in understanding how HIV-1 subviral complexes traverse an intracellular environment to complete the infection process by inserting proviral DNA into the host chromatin.…”

Section: Variability In Hiv-1 Utilization Of Capsid-dependent Host Proteinsmentioning

confidence: 99%

“…The N74D change modulates capsid interactions with other host factors as well. Recent work discovered that Sec24c is a novel capsid interacting protein that promotes early HIV-1 infection [ 190 ]. Remarkably, Sec24c binds CA at the binding interface utilized by CPSF6 and NUP153 [ 190 ].…”

Section: Variability In Hiv-1 Utilization Of Capsid-dependent Host Proteinsmentioning

confidence: 99%

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HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules

Saito

Yamashita

2021

Retrovirology

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The HIV-1 capsid, a conical shell encasing viral nucleoprotein complexes, is involved in multiple post-entry processes during viral replication. Many host factors can directly bind to the HIV-1 capsid protein (CA) and either promote or prevent HIV-1 infection. The viral capsid is currently being explored as a novel target for therapeutic interventions. In the past few decades, significant progress has been made in our understanding of the capsid–host interactions and mechanisms of action of capsid-targeting antivirals. At the same time, a large number of different viral capsids, which derive from many HIV-1 mutants, naturally occurring variants, or diverse lentiviruses, have been characterized for their interactions with capsid-binding molecules in great detail utilizing various experimental techniques. This review provides an overview of how sequence variation in CA influences phenotypic properties of HIV-1. We will focus on sequence differences that alter capsid–host interactions and give a brief account of drug resistant mutations in CA and their mutational effects on viral phenotypes. Increased knowledge of the sequence-function relationship of CA helps us deepen our understanding of the adaptive potential of the viral capsid.

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Section: Variability In Hiv-1 Utilization Of Capsid-dependent Host Proteinsmentioning

confidence: 99%

Section: Variability In Hiv-1 Utilization Of Capsid-dependent Host Proteinsmentioning

confidence: 99%

HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules

Saito

Yamashita

2021

Retrovirology

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“…One recent study found that the Sec24C, a protein involved in vesicular transport [ 90 ], interacts and cotraffics with HIV-1 IN and CA labeled complexes [ 91 ]. Depletion of Sec24C reduced RT, nuclear import and integration.…”

Section: Interplay Between Trn-sr2 and Cpsf6mentioning

confidence: 99%

“…A long-acting CA inhibitor with clinical potency has recently been reported [ 98 ]. Structural studies revealed that Sec24C, CPSF6, NUP153 and PF74 share the same binding interface on CA [ 91 ]. In conclusion, both the N74D mutation and the CA inhibitors have pleiotropic effects affecting the interaction of CA with consecutively Sec24C, Nup153 and CPSF6.…”

Section: Interplay Between Trn-sr2 and Cpsf6mentioning

confidence: 99%

Role of Transportin-SR2 in HIV-1 Nuclear Import

Tabasi

Nombela

Janssens

et al. 2021

Viruses

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The HIV replication cycle depends on the interaction of viral proteins with proteins of the host. Unraveling host–pathogen interactions during the infection is of great importance for understanding the pathogenesis and the development of antiviral therapies. To date HIV uncoating and nuclear import are the most debated steps of the HIV-1 replication cycle. Despite numerous studies during past decades, there is still much controversy with respect to the identity and the role of viral and host factors involved in these processes. In this review, we provide a comprehensive overview on the role of transportin-SR2 as a host cell factor during active nuclear transport.

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“…Rapid or gradual disassembly in the cytosol was also supported by several studies applying fluorescence imaging to analyze subviral complexes in infected cells (Hulme, Perez and Hope, 2011; Xu et al ., 2013; Cosnefroy, Murray and Bishop, 2016; Mamede et al ., 2017). However, the finding that CA, or even the capsid lattice, directly interacts with various host factors involved in post-entry replication steps - including not only cytosolic proteins but also nucleoporins and even the nuclear protein CPSF6 (e.g., Schaller et al ., 2011; Price et al ., 2012; Di Nunzio et al ., 2013; Matreyek et al ., 2013; Bhattacharya et al ., 2014; Lelek et al ., 2015; Rebensburg et al ., 2021) - implicated involvement of at least a partial lattice structure in later stages of post-entry replication. Furthermore, increasing evidence from imaging-based analyses argued for capsid uncoating at the nuclear pore (Arhel et al 2007; Burdick et al 2017; Rodriguez, Lester, and Dougherty 2007; Francis et al 2016; Francis and Melikyan 2018; Francis, Marin, Prellberg, et al 2020; Rasaiyaah et al 2013), or even for the passage of capsids or capsid-related structures through nuclear pores (Zila et al 2021; Selyutina et al 2020; T. G. Müller et al 2021; Dharan et al 2020; Burdick et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Direct capsid labeling of infectious HIV-1 by genetic code expansion allows detection of largely complete nuclear capsids and suggests nuclear entry of HIV-1 complexes via common routes

Schifferdecker

Žíla

Mueller

et al. 2021

Preprint

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The cone-shaped mature HIV-1 capsid is the main orchestrator of early viral replication. After cytosolic entry, it transports the viral replication complex along microtubules towards the nucleus. Capsid uncoating from the viral genome apparently occurs beyond the nuclear pore. Observation of post-entry events via microscopic detection of HIV-1 capsid protein (CA) is challenging, since epitope shielding limits immunodetection, and the genetic fragility of CA hampers other labeling approaches. Here, we present a minimally invasive strategy based on genetic code expansion and click chemistry that allows for site-directed fluorescent labeling of HIV-1 CA, while retaining virus morphology and infectivity. Thereby, we could directly visualize virions and subviral complexes using advanced microscopy, including nanoscopy and correlative imaging. Quantification of signal intensities of subviral complexes showed that the amount of CA associated with nuclear complexes in HeLa-derived cells and primary T cells is consistent with a complete capsid and revealed that treatment with the small molecule inhibitor PF74 did not result in capsid dissociation from nuclear complexes. Cone-shaped objects detected in the nucleus by electron tomography were clearly identified as capsid-derived structures by correlative microscopy. High-resolution imaging revealed dose-dependent clustering of nuclear capsids, suggesting that incoming particles may follow common entry routes.

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Sec24C is an HIV-1 host dependency factor crucial for virus replication

Cited by 64 publications

References 71 publications

HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules

HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules

Role of Transportin-SR2 in HIV-1 Nuclear Import

Direct capsid labeling of infectious HIV-1 by genetic code expansion allows detection of largely complete nuclear capsids and suggests nuclear entry of HIV-1 complexes via common routes

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