The Golgi associated ERI3 is a Flavivirus host factor

Ward, Alex M.; Calvert, Meredith; Read, Leah R.; Kang, Sang‐Wook; Levitt, Brandt; Dimopoulos, George; Bradrick, Shelton S.; Gunaratne, Jayantha; García-Blanco, Mariano A.

doi:10.1038/srep34379

Cited by 30 publications

(33 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We propose that this increased association between the ER and Golgi membrane compartments reflects the contribution of both types of membranes to the formation of the HCV MW/VRC. In accordance with this notion a recent study showed that the Golgi-associated protein ER13 is a dengue virus host factor that relocates to ER membranes during viral infection (36). These results demonstrate that Golgi-derived membranes/proteins are important for replication of Flaviviruses other than HCV and highlight the complexity of the cellular membrane structures supporting viral replication.…”

Section: Discussionsupporting

confidence: 67%

“…GBF1 and Arf1, proteins that conserve Golgi maintenance and function, are known to be crucial for the replication of certain RNA viruses, such as enteroviruses (17), possibly by recruitment of PI4KIIIβ to viral replication sites. Indeed, recent data have revealed that the Golgi membrane and Golgi proteins may have a previously unappreciated role in the replication of Enterovirus and Flavivirus (35,36). Moreover, GBF1 and Arf1 have been suggested to be host factors for HCV (18)(19)(20).…”

Section: Resultsmentioning

confidence: 99%

“…These results demonstrate that Golgi-derived membranes/proteins are important for replication of Flaviviruses other than HCV and highlight the complexity of the cellular membrane structures supporting viral replication. Similarly, other studies of membrane rearrangements during infection with Kunjin and West Nile virus suggest that Golgi proteins are indeed recruited to replication sites (36,47,48). Moreover, based on electron microscopy studies, it was suggested that Golgi membranes are the initial sites of poliovirus replication complexes (35).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M

Hansen

Johnsen

Stiberg

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

120

127

View full text Add to dashboard Cite

Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase M (IRGM), known to contribute to autophagy, plays a previously unrecognized role in this process. We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV. Our results show that IRGM controls phosphorylation of GBF1, a guanine nucleotide exchange factor for Arf-GTPases, which normally operates in Golgi membrane dynamics and vesicle coating in resting cells. We also find that HCV triggers IRGM-mediated phosphorylation of the early autophagy initiator ULK1, thereby providing mechanistic insight into the role of IRGM in HCV-mediated autophagy. Collectively, our results identify IRGM as a key Golgi-situated regulator that links intracellular membrane remodeling by autophagy and Golgi fragmentation with viral replication.HCV | Golgi fragmentation | autophagy | IRGM | membranous web H epatitis C virus (HCV) is a positive-sense RNA virus in the family Flaviviridae that is a major cause of chronic liver disease. All positive-strand RNA viruses studied until now, including HCV, replicate their genomes in association with cellular membrane rearrangements. In this process, viruses remodel intracellular membranes [e.g., of mitochondria, endoplasmic reticulum (ER), and plasma membrane] to generate membrane structures such as single-or double-membrane vesicles that contribute to viral replication complexes (VRCs). HCV replication takes place at a unique subcellular compartment, the membranous web (MW), which has been proposed to be derived from the ER (1, 2). The HCV MW has a complex morphology consisting of clusters of single-, double-, and multimembrane vesicles and probably includes autophagosomes and lipid droplets (1, 3, 4). Recent findings reveal that the MW is produced by distinct HCV nonstructural (NS) proteins acting through sequential interaction with several host factors, such as the virus-targeted phosphatidylinositol-4 kinase III α (PI4KIIIα) (2, 3), but the full spectrum of host components and precise membrane composition that supports HCV replication are not fully defined.Autophagy is an evolutionarily conserved cellular mechanism that involves intracellular membrane trafficking and degradation to maintain cell homeostasis. Viruses, including HCV, have been reported to exploit autophagy for replication purposes (4-6), but the mechanism by which this exploitation occurs is largely unknown. De novo synthesis of autophagosomes is a complex process that involves the formation of a phagophore membrane and its elongation. Initiation of autophagy is regulated by the mammalian target of rapamycin complex 1 (mTORC1), which neg...

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M

Hansen

Johnsen

Stiberg

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

120

127

View full text Add to dashboard Cite

show abstract

“…With that in mind, prediction of the possible folding of the homologous RNA structure of cis-acting RNA of each MBFV was done by the Mfold 1 . Remarkably, cis-acting RNAs can be a signal for antiviral or proviral cofactors in a structure dependent manner (Tables 1-3; Chahar et al, 2013;Li et al, 2013Phillips et al, 2016;Ward et al, 2016;Chavali et al, 2017;Chiu et al, 2018), which further indicated that RNAs share common evolutionary origins and contain frequent covariations to retain these RNA structures. In this sense, a comparative and thorough analysis on cis-acting RNA structures are needed to be conducted as means of identifying possible determinants of MBFV replication and pathogenicity.…”

Section: Introductionmentioning

confidence: 96%

Universal RNA Secondary Structure Insight Into Mosquito-Borne Flavivirus (MBFV) cis-Acting RNA Biology

et al. 2020

View full text Add to dashboard Cite

Mosquito-borne flaviviruses (MBFVs) spread between vertebrate (mammals and birds) and invertebrate (mosquitoes) hosts. The cis-acting RNAs of MBFV share common evolutionary origins and contain frequent alterations, which control the balance of linear and circular genome conformations and allow effective replication. Importantly, multiple cis-acting RNAs interact with transacting regulatory RNA-binding proteins (RBPs) and affect the MBFV lifecycle process, including viral replicase binding, viral RNA translation-cyclisation-synthesis and nucleocapsid assembly. Considering that extensive structural probing analyses have been performed on MBFV cis-acting RNAs, herein the homologous RNA structures are online folded and consensus structures are constructed by sort. The specific traits and underlying biology of MBFV cis-acting RNA are illuminated accordingly in a review of RNA structure. These findings deepen our understanding of MBFV cis-acting RNA biology and serve as a resource for designing therapeutics in targeting protein-viral RNA interaction or viral RNA secondary structures.

show abstract

“…Although it remains unclear whether PTB regulates DENV RNA simplification or Dengue -Immunopathology and Control Strategies the translation process (or another step of virus infection), PTB may function as a molecular chaperone to stabilize the structured viral RNA [30,31]. In addition to the host factors mentioned above, recent studies using tobramycin RNA aptamer affinity chromatography identified DDX6 (DEAD-box RNA helicase) and ERI3 (putative 3′-5′ RNA exonuclease) as DENV UTR-binding cellular proteins that promote DENV replication [32,33].…”

Section: Introductionmentioning

confidence: 99%

Cellular Control of Dengue Virus Replication: Role of Interferon-Inducible Genes

Takahashi¹,

Suzuki²

2017

Dengue - Immunopathology and Control Strategies

View full text Add to dashboard Cite

Dengue, one of the most common mosquito-borne viral infectious diseases in the world, is caused by the dengue virus (DENV). This enveloped RNA virus has immunologically distinct serotypes that increase the risk of life-threatening diseases, such as dengue haemorrhagic fever. However, no effective antiviral therapy against DENV infection has yet been established. As seen in other RNA viruses, various cellular factors have been reported to participate in efficient DENV replication. On the other hand, increasing recent evidence demonstrates that host cells harbour inhibitory factors that limit the DENV replication. In particular, it is well known that the response of interferons (IFNs), the first line of a host defence system against invading pathogens, evokes the expression of a number of genes that negatively regulate various steps of virus replication. This set of inhibitory genes, called interferon-stimulated genes (ISGs), is considered to be a central force in IFN-mediated antiviral responses. In this chapter, we focus our attention on the cellular factors involved in DENV infection, particularly to those that modulate DENV replication through their association with viral RNA. In addition, we also summarize general experimental approaches for identifying the host factors of RNA viruses, including DENV.life-threatening diseases in humans, such as haemorrhagic fever, encephalitis, and meningitis [2]. Recently, the Zika virus (ZIKV), a member of the flavivirus family that has spread explosively throughout the Americas, is reported to be associated with neurological complications [3,4]. Flaviviruses, therefore, have significant clinical as well as economic impacts on modern society.DENV is a mosquito-borne virus widely distributed in the tropical and subtropical areas of the world. This flavivirus infection is transmitted to humans via the bite of infected mosquitos. The primary vector of DENV infection is Aedes aegypti, while Aedes albopictus, which originated in Asia but has extended its range to other regions of the world, is also capable of spreading a dengue outbreak. DENV has four antigenically distinct serotypes (from DENV-1 to . Primary infection with one of the serotypes is often asymptomatic or causes selflimiting dengue fever (DF). However, secondary infection of different serotypes increases the risk of more serious forms of DENV infection, such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), due to the presence of non-or sub-neutralizing antibodies generated during the primary infection. Therefore, dengue is a significant threat to humans, yet there is currently no specific antiviral available for DENV infection [1,5]. However, it should be noted that a live attenuated vaccine against DENV developed by Sanofi Pasteur (Dengvaxia) has been licensed for use in a limited number of countries, including Mexico and the Philippines, although the efficacy of the DENV vaccine in endemic countries is still under investigation [6]. Brief overview of DENV replicationDENV infection begins with it...

show abstract

The Golgi associated ERI3 is a Flavivirus host factor

Cited by 30 publications

References 38 publications

Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M

Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M

Universal RNA Secondary Structure Insight Into Mosquito-Borne Flavivirus (MBFV) cis-Acting RNA Biology

Cellular Control of Dengue Virus Replication: Role of Interferon-Inducible Genes

Contact Info

Product

Resources

About