Key interplay between the co-opted sorting nexin-BAR proteins and PI3P phosphoinositide in the formation of the tombusvirus replicase

Feng, Zhike; Kovalev, Nikolay; Nagy, Peter D.

doi:10.1371/journal.ppat.1009120

Cited by 18 publications

(15 citation statements)

References 76 publications

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“…Asuka et al have previously reported co-localization of fluorescently-labeled EBOV particles with SNX5 in the process of researching the internalization mechanism of EBOV [ 252 ]. In addition, SNX5 and PI (3) P play a key role in the formation of the viral replicase complexes (VRCs) bound on the organelle membrane of the tomato bushy stunt virus (TBSV) [ 253 ]. Importantly, HCMV-encoded UL35 binds to and negatively regulates SNX5, thereby regulating cellular transport pathways that affect the virus assembly process [ 254 ].…”

Section: Virus-specific Induction Of Autophagymentioning

confidence: 99%

The role of autophagy in viral infections

Chen

Ding

et al. 2023

J Biomed Sci

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Autophagy is an evolutionarily conserved catabolic cellular process that exerts antiviral functions during a viral invasion. However, co-evolution and co-adaptation between viruses and autophagy have armed viruses with multiple strategies to subvert the autophagic machinery and counteract cellular antiviral responses. Specifically, the host cell quickly initiates the autophagy to degrade virus particles or virus components upon a viral infection, while cooperating with anti-viral interferon response to inhibit the virus replication. Degraded virus-derived antigens can be presented to T lymphocytes to orchestrate the adaptive immune response. Nevertheless, some viruses have evolved the ability to inhibit autophagy in order to evade degradation and immune responses. Others induce autophagy, but then hijack autophagosomes as a replication site, or hijack the secretion autophagy pathway to promote maturation and egress of virus particles, thereby increasing replication and transmission efficiency. Interestingly, different viruses have unique strategies to counteract different types of selective autophagy, such as exploiting autophagy to regulate organelle degradation, metabolic processes, and immune responses. In short, this review focuses on the interaction between autophagy and viruses, explaining how autophagy serves multiple roles in viral infection, with either proviral or antiviral functions.

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Section: Virus-specific Induction Of Autophagymentioning

confidence: 99%

The role of autophagy in viral infections

Chen

Ding

et al. 2023

J Biomed Sci

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“…VRO formation requires subversion of several membranous compartments and vesicles as well as numerous co-opted cytosolic host proteins [2,3,[5][6][7][8][71][72][73][74]. Indeed, tombusviruses co-opt cellular membranous carriers, such as retromer-based tubular carriers, COPII vesicles and their selected cargoes via p33-based targeting of cellular membrane proteins, such as Rab1 and Rab5 small GTPases or the retromer complex and delivering them to the VROs for various functions and membrane modifications and membrane proliferation [51,52,[75][76][77]. Another major function of p33 is the selection of the TBSV (+)RNA for replication and recruitment into VROs [32,78].…”

Section: Discussionmentioning

confidence: 99%

A novel viral strategy for host factor recruitment: The co-opted proteasomal Rpn11 protein interaction hub in cooperation with subverted actin filaments are targeted to deliver cytosolic host factors for viral replication

2021

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Positive-strand (+)RNA viruses take advantage of the host cells by subverting a long list of host protein factors and transport vesicles and cellular organelles to build membranous viral replication organelles (VROs) that support robust RNA replication. How RNA viruses accomplish major recruitment tasks of a large number of cellular proteins are intensively studied. In case of tomato bushy stunt virus (TBSV), a single viral replication protein, named p33, carries out most of the recruitment duties. Yet, it is currently unknown how the viral p33 replication protein, which is membrane associated, is capable of the rapid and efficient recruitment of numerous cytosolic host proteins to facilitate the formation of large VROs. In this paper, we show that, TBSV p33 molecules do not recruit each cytosolic host factor one-by-one into VROs, but p33 targets a cytosolic protein interaction hub, namely Rpn11, which interacts with numerous other cytosolic proteins. The highly conserved Rpn11, called POH1 in humans, is the metalloprotease subunit of the proteasome, which couples deubiquitination and degradation of proteasome substrates. However, TBSV takes advantage of a noncanonical function of Rpn11 by exploiting Rpn11’s interaction with highly abundant cytosolic proteins and the actin network. We provide supporting evidence that the co-opted Rpn11 in coordination with the subverted actin network is used for delivering cytosolic proteins, such as glycolytic and fermentation enzymes, which are readily subverted into VROs to produce ATP locally in support of VRO formation, viral replicase complex assembly and viral RNA replication. Using several approaches, including knockdown of Rpn11 level, sequestering Rpn11 from the cytosol into the nucleus in plants or temperature-sensitive mutation in Rpn11 in yeast, we show the inhibition of recruitment of glycolytic and fermentation enzymes into VROs. The Rpn11-assisted recruitment of the cytosolic enzymes by p33, however, also requires the combined and coordinated role of the subverted actin network. Accordingly, stabilization of the actin filaments by expression of the Legionella VipA effector in yeast and plant, or via a mutation of ACT1 in yeast resulted in more efficient and rapid recruitment of Rpn11 and the selected glycolytic and fermentation enzymes into VROs. On the contrary, destruction of the actin filaments via expression of the Legionella RavK effector led to poor recruitment of Rpn11 and glycolytic and fermentation enzymes. Finally, we confirmed the key roles of Rpn11 and the actin filaments in situ ATP production within TBSV VROs via using a FRET-based ATP-biosensor. The novel emerging theme is that TBSV targets Rpn11 cytosolic protein interaction hub driven by the p33 replication protein and aided by the subverted actin filaments to deliver several co-opted cytosolic pro-viral factors for robust replication within VROs.

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“…The functions of these host factors range from having direct roles in altering membrane structures to indirect roles in forming the specific membrane or lipid environments required for virus-driven processes. For instance, the membrane shaping functions of ESCRT proteins and BAR domain containing proteins are involved for TBSV vROs biogenesis [7][8][9]. TBSV-induced peroxisome:ER membrane contact sites contain several lipid metabolism or transfer proteins that facilitate movement of lipid species between these membrane domains, likely providing lipids required for replication.…”

Section: Structure and Biogenesis: Insights From Model Virusesmentioning

confidence: 99%

Membrane architects: how positive-strand RNA viruses restructure the cell

Neufeldt

Cortese

2022

Journal of General Virology

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Virus infection is a process that requires combined contributions from both virus and host factors. For this process to be efficient within the crowded host environment, viruses have evolved ways to manipulate and reorganize host structures to produce cellular microenvironments. Positive-strand RNA virus replication and assembly occurs in association with cytoplasmic membranes, causing a reorganization of these membranes to create microenvironments that support viral processes. Similarities between virus-induced membrane domains and cellular organelles have led to the description of these structures as virus replication organelles (vRO). Electron microscopy analysis of vROs in positive-strand RNA virus infected cells has revealed surprising morphological similarities between genetically diverse virus species. For all positive-strand RNA viruses, vROs can be categorized into two groups: those that make invaginations into the cellular membranes (In-vRO), and those that cause the production of protrusions from cellular membranes (Pr-vRO), most often in the form of double membrane vesicles (DMVs). In this review, we will discuss the current knowledge on the structure and biogenesis of these two different vRO classes as well as comparing morphology and function of vROs between various positive-strand RNA viruses. Finally, we will discuss recent studies describing pharmaceutical intervention in vRO formation as an avenue to control virus infection.

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Key interplay between the co-opted sorting nexin-BAR proteins and PI3P phosphoinositide in the formation of the tombusvirus replicase

Cited by 18 publications

References 76 publications

The role of autophagy in viral infections

The role of autophagy in viral infections

A novel viral strategy for host factor recruitment: The co-opted proteasomal Rpn11 protein interaction hub in cooperation with subverted actin filaments are targeted to deliver cytosolic host factors for viral replication

Membrane architects: how positive-strand RNA viruses restructure the cell

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