Mini-genome rescue of Crimean-Congo hemorrhagic fever virus and research into the evolutionary patterns of its untranslated regions

Zhao, Jianan; Xia, Han; Zhāng, Yújiāng; Yin, Shiyu; Zhang, Zhong; Táng, Shuāng; Kou, Zheng; Yu, Jiang; Fan, Zhenzhen; Li, Tianxian

doi:10.1016/j.virusres.2013.07.005

Cited by 2 publications

(3 citation statements)

References 37 publications

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“…CCHFV tcVLPs were capable of primary transcription, which is detectable when the REN-Luc reporter is expressed via the strong L segment promoter. This demonstrates that the L polymerase packaged into the VLPs is active and confirms previous observations on the high activity of the bunyaviral L promoter (14,16,36,37). Using a tc-VLP system for RVFV, we have previously shown that primary transcription is sufficient to trigger innate immune responses mediated by the pathogen recognition receptor RIG-I (38) and that the antiviral host cell protein MxA is targeting RVFV primary transcription (18).…”

Section: Generation Of Cchf Virus-like Particles Expressing a Reportesupporting

confidence: 89%

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A Virus-Like Particle System Identifies the Endonuclease Domain of Crimean-Congo Hemorrhagic Fever Virus

Devignot

Bergeron

Nichol

et al. 2015

J Virol

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Crimean-Congo hemorrhagic fever virus (CCHFV; genus Nairovirus) is an extremely pathogenic member of the Bunyaviridae family. Since handling of the virus requires a biosafety level 4 (BSL-4) facility, little is known about pathomechanisms and host interactions. Here, we describe the establishment of a transcriptionally competent virus-like particle (tc- VLP IMPORTANCECrimean-Congo hemorrhagic fever virus (CCHFV) is an extremely virulent pathogen of humans. Since the virus can be handled only at the highest biosafety level, research is restricted to a few specialized laboratories. We developed a plasmid-based system to produce virus-like particles with the ability to infect cells and transcribe a reporter genome. Due to the absence of viral genes, the virus-like particles are unable to spread or cause disease, thus allowing study of aspects of CCHFV biology under relaxed biosafety conditions. C rimean-Congo hemorrhagic fever (CCHF) is a severe viral disease in Eastern Europe, the Middle East, Asia, and Africa, reported to have a case/fatality rate of approximately 30% (1). Infections of humans are associated with an acute febrile disease that can lead to hemorrhages, hypovolemic shock, and death, while in infected animals no clinical signs can be detected. The CCHF virus (CCHFV) is transmitted via tick bites (principally from the Hyalomma genus) or by direct contact with blood or tissues from infected persons or animals (2). The efficiency of ribavirin as an antiviral in humans is still under debate (3), and there are currently no established prophylaxis, no specific treatment, and no FDA-approved vaccine. The pathogenesis as well as immune responses are poorly characterized, mostly due to the restriction to high-biosafety-level facilities (biosafety level 4 [BSL-4]) for handling of virus and biological samples. The only animal models available so far are based on mice lacking antiviral interferon (IFN) responses, thus hampering studies on innate immune system interactions (4, 5). Clearly, there is paucity in tools and methods to better study the virus and its host cell interactions.CCHFV belongs to the Nairovirus genus of the family Bunyaviridae. This enveloped virus has a single-stranded negative-sense RNA genome (viral RNA [vRNA]) of an unusually large total size of 19,146 nucleotides (nt). The genome is divided into 3 segments and encodes 4 structural proteins: the RNA-dependent RNA polymerase (RdRp) L on the large (L) segment (12,108 nt), the two glycoproteins (GPs) Gc and Gn on the medium (M) segment (5,366 nt), and the nucleoprotein N on the small (S) segment (1,672 nt). The nucleoprotein N binds each RNA segment to form ribonucleoprotein complexes (RNPs), the functional template of the viral polymerase (pol) L for transcription and replication. Shortly after infection, CCHFV performs the so-called primary transcription leading to initial mRNA synthesis. The protein products are necessary for subsequent replication of the viral genome, resulting in copy RNA (cRNA) (positive sense) and progeny genom...

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Section: Generation Of Cchf Virus-like Particles Expressing a Reportesupporting

confidence: 89%

“…2A, lanes 1 and 3). The CCHFV glycoproteins Gn and Gc, as well as nucleoprotein N, can be detected approximately at their expected size (37,75, and 54 kDa, respectively) in both virus and tc-VLP supernatants ( Fig. 2A, lanes 2 and 6).…”

Section: Generation Of Cchf Virus-like Particles Expressing a Reportementioning

confidence: 92%

A Virus-Like Particle System Identifies the Endonuclease Domain of Crimean-Congo Hemorrhagic Fever Virus

Devignot

Bergeron

Nichol

et al. 2015

J Virol

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“…The MG system has been mainly used to examine the cis - and trans -acting factors involved in bunyavirus replication and transcription ( Barr et al, 2003 ; Ikegami et al, 2005 ), defining the minimal cis - and trans -acting factors required for viral replication ( Barr et al, 2003 ), mapping critical residues of the viral promoter ( Flick et al, 2004 ; Zhao et al, 2013 ), exploring the packaging ( Kohl et al, 2006 ), revealing the pathogenic mechanism ( Ruiz-Jarabo et al, 2003 ; Shao et al, 2018 ), and identifying novel antiviral compounds ( Rathbun et al, 2015 ) without requiring the use of live forms of bunyaviruses. For example, Flick et al created the first pol-I-driven MG system of HTNV (Hantaviridae) in 2003, which provided powerful tools for studying the functions of essential genes or proteins of hantavirus ( Flick et al, 2003 ).…”

Section: Development and Application Of Reverse Genetic Systems For Bunyavirusesmentioning

confidence: 99%

Recent Advances in Bunyavirus Reverse Genetics Research: Systems Development, Applications, and Future Perspectives

et al. 2021

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Bunyaviruses are members of the Bunyavirales order, which is the largest group of RNA viruses, comprising 12 families, including a large group of emerging and re-emerging viruses. These viruses can infect a wide variety of species worldwide, such as arthropods, protozoans, plants, animals, and humans, and pose substantial threats to the public. In view of the fact that a better understanding of the life cycle of a highly pathogenic virus is often a precondition for developing vaccines and antivirals, it is urgent to develop powerful tools to unravel the molecular basis of the pathogenesis. However, biosafety level −3 or even −4 containment laboratory is considered as a necessary condition for working with a number of bunyaviruses, which has hampered various studies. Reverse genetics systems, including minigenome (MG), infectious virus-like particle (iVLP), and infectious full-length clone (IFLC) systems, are capable of recapitulating some or all steps of the viral replication cycle; among these, the MG and iVLP systems have been very convenient and effective tools, allowing researchers to manipulate the genome segments of pathogenic viruses at lower biocontainment to investigate the viral genome transcription, replication, virus entry, and budding. The IFLC system is generally developed based on the MG or iVLP systems, which have facilitated the generation of recombinant infectious viruses. The MG, iVLP, and IFLC systems have been successfully developed for some important bunyaviruses and have been widely employed as powerful tools to investigate the viral replication cycle, virus–host interactions, virus pathogenesis, and virus evolutionary process. The majority of bunyaviruses is generally enveloped negative-strand RNA viruses with two to six genome segments, of which the viruses with bipartite and tripartite genome segments have mostly been characterized. This review aimed to summarize current knowledge on reverse genetic studies of representative bunyaviruses causing severe diseases in humans and animals, which will contribute to the better understanding of the bunyavirus replication cycle and provide some hints for developing designed antivirals.

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Mini-genome rescue of Crimean-Congo hemorrhagic fever virus and research into the evolutionary patterns of its untranslated regions

Cited by 2 publications

References 37 publications

A Virus-Like Particle System Identifies the Endonuclease Domain of Crimean-Congo Hemorrhagic Fever Virus

A Virus-Like Particle System Identifies the Endonuclease Domain of Crimean-Congo Hemorrhagic Fever Virus

Recent Advances in Bunyavirus Reverse Genetics Research: Systems Development, Applications, and Future Perspectives

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