Identification of GBF1 as a cellular factor required for hepatitis E virus RNA replication

Farhat, Rayan; Ankavay, Maliki; Lebsir, Nadjet; Gouttenoire, Jérôme; Jackson, Catherine; Wychowski, Czeslaw; Moradpour, Darius; Dubuisson, Jean; Rouillé, Yves; Cocquerel, Laurence

doi:10.1111/cmi.12804

Cited by 30 publications

(30 citation statements)

References 46 publications

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“…Interestingly, BFA and GCA inhibit the development of infection when added early during the infection cycle but rapidly lose their effectiveness if added after ~12 h, at the time of active virion maturation and release [ 96 , 98 ]. This may suggest that GBF1 is involved not only in the early steps of virion assembly by regulating the availability of the capsid protein but also may support Zika RNA replication directly, as has been described for many diverse (+)RNA viruses [ 108 , 109 , 110 , 111 , 112 ].…”

Section: The Secretory Pathway In Zika Virus Infection: Moving Thrmentioning

confidence: 75%

Role of Host Cell Secretory Machinery in Zika Virus Life Cycle

Sager

Gabaglio

Sztul

et al. 2018

Viruses

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The high human cost of Zika virus infections and the rapid establishment of virus circulation in novel areas, including the United States, present an urgent need for countermeasures against this emerging threat. The development of an effective vaccine against Zika virus may be problematic because of the cross reactivity of the antibodies with other flaviviruses leading to antibody-dependent enhancement of infection. Moreover, rapidly replicating positive strand RNA viruses, including Zika virus, generate large spectrum of mutant genomes (quasi species) every replication round, allowing rapid selection of variants resistant to drugs targeting virus-specific proteins. On the other hand, viruses are ultimate cellular parasites and rely on the host metabolism for every step of their life cycle, thus presenting an opportunity to manipulate host processes as an alternative approach to suppress virus replication and spread. Zika and other flaviviruses critically depend on the cellular secretory pathway, which transfers proteins and membranes from the ER through the Golgi to the plasma membrane, for virion assembly, maturation and release. In this review, we summarize the current knowledge of interactions of Zika and similar arthropod-borne flaviviruses with the cellular secretory machinery with a special emphasis on virus-specific changes of the secretory pathway. Identification of the regulatory networks and effector proteins required to accommodate the trafficking of virions, which represent a highly unusual cargo for the secretory pathway, may open an attractive and virtually untapped reservoir of alternative targets for the development of superior anti-viral drugs.

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Section: The Secretory Pathway In Zika Virus Infection: Moving Thrmentioning

confidence: 75%

Role of Host Cell Secretory Machinery in Zika Virus Life Cycle

Sager

Gabaglio

Sztul

et al. 2018

Viruses

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“…The negative strand RNA virus vesicular stomatitis virus (VSV), but also the non-enveloped RNA viruses Coxsackievirus B and hepatitis E virus, similarly depend on GBF1 for their genome replication (24)(25)(26). Despite the fact that a range of RNA viruses hijacks GBF1 for genome replication complex formation, we currently lack knowledge whether GBF1 plays a role in replication or assembly and release of negative strand RNA viruses of the Phenuiviridae family in the Bunyavirales order.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses

Uckeley

Moeller

Kühn

et al. 2019

Molecular & Cellular Proteomics

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Novel tick-borne phleboviruses in the Phenuiviridae family, which are highly pathogenic in humans and all closely related to Uukuniemi virus (UUKV), have recently emerged on different continents. How phleboviruses assemble, bud, and exit cells remains largely elusive. Here, we performed high-resolution, label-free mass spectrometry analysis of UUKV immuno-precipitated from cell lysates and identified 39 cellular partners interacting with the viral envelope glycoproteins. The importance of these host factors for UUKV infection was validated by silencing each host factor by RNA interference. This revealed Golgi-specific brefeldin Aresistance guanine nucleotide exchange factor 1 (GBF1), a guanine nucleotide exchange factor resident in the Golgi, as a critical host factor required for the UUKV life cycle. An inhibitor of GBF1, Golgicide A, confirmed the role of the cellular factor in UUKV infection. We could pinpoint the GBF1 requirement to UUKV replication and particle assembly. When the investigation was extended to viruses from various positive and negative RNA viral families, we found that not only phleboviruses rely on GBF1 for infection, but also Flavi-, Corona-, Rhabdo-, and Togaviridae. In contrast, silencing or blocking GBF1 did not abrogate infection by the human adenovirus serotype 5 and immunodeficiency retrovirus type 1, the replication of both occurs in the nucleus. Together our results indicate that UUKV relies on GBF1 for viral replication, assembly and egress. This study also highlights the proviral activity of GBF1 in the infection by a broad range of important zoonotic RNA viruses.

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“…For example, Guanyl-nucleotide exchange factor (GEF) (GO:0005086) was proved as an essential factor for hepatitis E virus replication [24]. In plant virus as well, the involvement of GEF in the translation initiation process was proved via mutation studies on turnip mosaic virus (TuMV) [25].…”

Section: Target Predictionsmentioning

confidence: 99%

Prediction and experimental confirmation of banana bract mosaic virus encoding miRNAs and their targets

Sankaranarayanan

Palani

Kumar

et al. 2020

ExRNA

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Background: Potyviridae is the largest plant infecting family under the monophyletic group Riboviria, infects many of the food, fodder and ornamental crops. Due to the higher mutation and recombination rate, potyvirids are evolving rapidly, adapting to the environmental chaos and expanding their hosts. Virus control measures are need to be updated as the economic importance of potyvirids is massive. microRNAs (miRNAs) are well known for their functional importance in eukaryotes and many viruses. Regardless of its biogenesis, whether canonical or noncanonical, microRNA centric antivirus approaches attract the researchers to the hopeful future of nextgeneration broad-spectrum antiviral measures. Methods: In this study, we predicted and screened banana bract mosaic virus (BBrMV) encoding miRNAs by computation approaches and their targets on banana transcriptome using plant small RNA target analysis server (psRNAtarget). The target gene functions were annotated by Blast2GO. The predicted BBrMV miRNAs were experimentally screened by stem-loop RT-PCR. Results: The results showed that, among the predicted BBrMV miRNAs, miRNA2 is conserved throughout BBrMV isolates and has multiple virus-specific target transcripts. In addition, primary experimental validation for the predicted miRNAs revealed that miRNA2 exists in the BBrMV infected banana leaf samples. Conclusions: The existence of BBrMV miRNA2 is confirmed by stem-loop RT-PCR followed by cloning and sequencing. The presence of miRNA of Potyviridae is rarely addressed and would definitely spread the hope to understand the virus infectious cycle. Our report would also help to better understand and manipulate potyviral infections.

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Identification of GBF1 as a cellular factor required for hepatitis E virus RNA replication

Cited by 30 publications

References 46 publications

Role of Host Cell Secretory Machinery in Zika Virus Life Cycle

Role of Host Cell Secretory Machinery in Zika Virus Life Cycle

Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses

Prediction and experimental confirmation of banana bract mosaic virus encoding miRNAs and their targets

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