An essential receptor for adeno-associated virus infection

Pillay, Sureshnee; Meyer, Nancy; Puschnik, Andreas S.; Davulcu, Omar; Diep, Jonathan; Ishikawa, Yoshihiro; Jae, Lucas T.; Wosen, Jonathan; Nagamine, Claude M.; Chapman, Michael S.; Carette, Jan E.

doi:10.1038/nature16465

Cited by 390 publications

(489 citation statements)

References 31 publications

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“…Firstly, we found that both ORF7 and ORF53 co-localized well with the TGN46 protein ( Figure 3A and 3B), which is widely used as a TGN marker in numerous studies (Barr et al, 2010;Donsante et al, 2011;Zhao et al, 2012;Charles et al, 2014;Nonnenmacher et al, 2015;Pillay et al, 2016). The Pearson's coefficients were 0.70 ± 0.09 and 0.68 ± 0.08 in the co-localized volume of TGN46 with ORF7 and ORF53, respectively (n = 10 in each group).…”

Section: Orf7 Co-localizes With Orf53 In the Tgn Of Infected Cellsmentioning

confidence: 79%

Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization

Wang

Pan

et al. 2017

Virol. Sin.

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Varicella-zoster virus (VZV) is a neurotropic alphaherpesvirus that causes chickenpox andshingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues, however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 kDa viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis. KEYWORDSvaricella-zoster virus (VZV); ORF7; ORF53; protein-protein interaction; trans-Golgi network

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Section: Orf7 Co-localizes With Orf53 In the Tgn Of Infected Cellsmentioning

confidence: 79%

Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization

Wang

Pan

et al. 2017

Virol. Sin.

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“…Viral vectors are proving to be a highly effective modality for gene therapy, and the adeno-associated virus (AAV) is currently a preferred platform for many in vivo gene transfer applications. The AAV capsid serves as the interface between the therapeutic transgene and the host, interacting with host cell machinery and performing functions to accomplish a transduction event, including attachment to host cell glycans (Bell et al, 2012; Kern et al, 2003; Wu et al, 2000), binding to cell surface receptor(s) (e.g., AAVR) to trigger its endocytosis (Pillay et al, 2016), endosomal escape (Girod et al, 2002), trafficking to the nucleus (Grieger et al, 2006), entry through the nuclear pore complex (Nicolson and Samulski, 2014), and uncoating the single-stranded DNA (ssDNA) genome in the nucleoplasm (Thomas et al, 2004). While the capsid enacts these processes, it maintains the integrity of its genomic cargo, protecting it from both the host cellular milieu and the external environment.…”

Section: Introductionmentioning

confidence: 99%

The Assembly-Activating Protein Promotes Stability and Interactions between AAV’s Viral Proteins to Nucleate Capsid Assembly

et al. 2018

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SUMMARY The adeno-associated virus (AAV) vector is a preferred delivery platform for in vivo gene therapy. Natural and engineered variations of the AAV capsid affect a plurality of phenotypes relevant to gene therapy, including vector production and host tropism. Fundamental to these aspects is the mechanism of AAV capsid assembly. Here, the role of the viral co-factor assembly-activating protein (AAP) was evaluated in 12 naturally occurring AAVs and 9 putative ancestral capsid intermediates. The results demonstrate increased capsid protein stability and VP-VP interactions in the presence of AAP. The capsid’s dependence on AAP can be partly overcome by strengthening interactions between monomers within the assembly, as illustrated by the transfer of a minimal motif defined by a phenotype-to-phylogeny mapping method. These findings suggest that the emergence of AAP within the Dependovirus genus relaxes structural constraints on AAV assembly in favor of increasing the degrees of freedom for the capsid to evolve.

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“…In recent years, genome-wide knockout (KO) screens in human haploid cells—and most recently, CRISPR KO screens in a variety of cells—have been used to identify host factors required by several viruses from different families e.g. Arenaviridae , Bunyaviridae , Filoviridae , Flaviviridae , Orthomyxoviridae and Parvoviridae (Carette et al, 2009; Carette et al, 2011; Jae et al, 2014; Jae et al, 2013; Marceau et al, 2016; Pillay et al, 2016; Riblett et al, 2016; Savidis et al, 2016; Zhang et al, 2016). In all cases, genes that are essential for N-linked glycosylation were highly enriched in the screens.…”

Section: Introductionmentioning

confidence: 99%

Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

Hoffmann

Schneider

Blomen

et al. 2017

Cell Host & Microbe

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SUMMARY Respiratory and arthropod-borne viral infections are a global threat due to the lack of effective antivirals and vaccines. A potential strategy is to target host proteins required for viruses but non-essential for the host. To identify such proteins, we performed a genome-wide knockout screen in human haploid cells and identified the calcium pump SPCA1. SPCA1 is required by viruses from the Paramyxo-, Flavi-, and Togaviridae families, including measles, dengue, West Nile, Zika, and chikungunya viruses. Calcium transport activity is required for SPCA1 to promote virus spread. SPCA1 regulates proteases within the trans-Golgi network that require calcium for their activity and are critical for virus glycoprotein maturation. Consistent with these findings, viral glycoproteins fail to mature in SPCA1-deficient cells preventing viral spread, which is evident even in cells with partial loss of SPCA1. Thus, SPCA1 is an attractive antiviral host target for a broad spectrum of established and emerging viral infections.

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An essential receptor for adeno-associated virus infection

Cited by 390 publications

References 31 publications

Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization

Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization

The Assembly-Activating Protein Promotes Stability and Interactions between AAV’s Viral Proteins to Nucleate Capsid Assembly

Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

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