Global Suppression of the Host Antiviral Response by Ebola- and Marburgviruses: Increased Antagonism of the Type I Interferon Response Is Associated with Enhanced Virulence

Kash, John C.; Mühlberger, Elke; Carter, Victoria; Grosch, Melanie N.; Perwitasari, Olivia; Proll, Sean; Thomas, Matthew; Weber, Friedemann; Klenk, Hans Dieter; Katze, Michael G.

doi:10.1128/jvi.80.6.3009-3020.2006

Cited by 168 publications

(198 citation statements)

References 43 publications

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“…It is already known for the polymerase cofactor VP35 that it interferes with the innate immune system [26][27][28]. Within the same vein, bioinformatic analysis has revealed that filovirus species differing in their replication efficiency also differ in their ability to evade the cellular antiviral response [71].…”

Section: Future Perspectivementioning

confidence: 96%

Filovirus Replication and Transcription

2007

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The highly pathogenic filoviruses, Marburg and Ebola virus, belong to the nonsegmented negative-sense RNA viruses of the order Mononegavirales. The mode of replication and transcription is similar for these viruses. On one hand, the negative-sense RNA genome serves as a template for replication, to generate progeny genomes, and, on the other hand, for transcription, to produce mRNAs. Despite the similarities in the replication/transcription strategy, filoviruses have evolved structural and functional properties that are unique among the nonsegmented negativesense RNA viruses. Moreover, there are also striking differences in the replication and transcription mechanisms of Marburg and Ebola virus. This includes nucleocapsid formation, the structure of the genomic replication promoter, the protein requirement for transcription and the use of mRNA editing. In this article, the current knowledge of the replication and transcription strategy of Marburg and Ebola virus is reviewed, with focus on the observed differences.

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Section: Future Perspectivementioning

confidence: 96%

Filovirus Replication and Transcription

2007

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“…Moreover, the effects of VP35, VP24 and perhaps other filoviral proteins might prove even more pleiotropic -not only IFN-related genes but also multiple cellular genes were perturbed by filoviral infection of hepatocytes, many of these genes were differently dysregulated depending on the filovirus species 28 . Further, it was shown previously that interleukin-8 (IL-8; also known as CXC-chemokine ligand 8 (CXCL8)), an α-chemokine produced abundantly during filoviral infection, antagonizes the antiviral activity of IFNα by inhibiting the function of 2′,5′-oligoadenylate synthetase (OAS) in encephalomyocarditis virus (EMCV) infection 29 .…”

Section: Box 1 | Filovirus-disease Basicsmentioning

confidence: 99%

How Ebola and Marburg viruses battle the immune system

2007

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PantropicTending towards the capacity to infect a wide range of cells and organs. CoagulopathyRefers to a group of conditions of the blood-clotting system in which bleeding is prolonged and excessive. Cell tropismA virus's affinity for or tendency towards preferential infection of certain cells. How Ebola and Marburg viruses battle the immune systemMansour Mohamadzadeh* ‡ , Lieping Chen ‡ , and Alan L. Schmaljohn* Abstract | The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself. R E V I E W S Report Documentation PageForm Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.

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“…93 In addition, RESTV GP shows lower ability to deplete T cells and to down-regulate interferon-stimulated gene expression compared to ZEBOV GP. 94,95 Meanwhile, ZEBOV VP35 shows stronger Interferon inhibition than RESTV VP35 in human cells. 68 However, direct studies of all RESTV proteins' effect in cells of both RESTV-susceptible and RESTV-resistant species are needed to prove our hypothesis.…”

Section: The Zinc-finger Domain Of Vp30mentioning

confidence: 99%

Predictive and comparative analysis of Ebolavirus proteins

2015

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Ebolavirus is the pathogen for Ebola Hemorrhagic Fever (EHF). This disease exhibits a high fatality rate and has recently reached a historically epidemic proportion in West Africa. Out of the 5 known Ebolavirus species, only Reston ebolavirus has lost human pathogenicity, while retaining the ability to cause EHF in long-tailed macaque. Significant efforts have been spent to determine the three-dimensional (3D) structures of Ebolavirus proteins, to study their interaction with host proteins, and to identify the functional motifs in these viral proteins. Here, in light of these experimental results, we apply computational analysis to predict the 3D structures and functional sites for Ebolavirus protein domains with unknown structure, including a zinc-finger domain of VP30, the RNA-dependent RNA polymerase catalytic domain and a methyltransferase domain of protein L. In addition, we compare sequences of proteins that interact with Ebolavirus proteins from RESTV-resistant primates with those from RESTV-susceptible monkeys. The host proteins that interact with GP and VP35 show an elevated level of sequence divergence between the RESTV-resistant and RESTV-susceptible species, suggesting that they may be responsible for host specificity. Meanwhile, we detect variable positions in protein sequences that are likely associated with the loss of human pathogenicity in RESTV, map them onto the 3D structures and compare their positions to known functional sites. VP35 and VP30 are significantly enriched in these potential pathogenicity determinants and the clustering of such positions on the surfaces of VP35 and GP suggests possible uncharacterized interaction sites with host proteins that contribute to the virulence of Ebolavirus.

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Global Suppression of the Host Antiviral Response by Ebola- and Marburgviruses: Increased Antagonism of the Type I Interferon Response Is Associated with Enhanced Virulence

Cited by 168 publications

References 43 publications

Filovirus Replication and Transcription

Filovirus Replication and Transcription

How Ebola and Marburg viruses battle the immune system

Predictive and comparative analysis of Ebolavirus proteins

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