A newly discovered flavivirus in the yellow fever virus group displays restricted replication in vertebrates

Colmant, Agathe M. G.; Bielefeldt‐Ohmann, Helle; Hobson‐Peters, Jody; Suen, Willy W.; O’Brien, Caitlin A.; Hurk, Andrew F. van den; Hall, Roy A.

doi:10.1099/jgv.0.000430

Cited by 27 publications

(45 citation statements)

References 43 publications

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“…The pr-M furin cleavage site for KRBV, McPV, and HaCV occurs between amino acids 172 and 173 and follows the consensus established for other flaviviruses (23), suggesting that the cleavage is efficient, unlike for some cISFs (e.g., PaRV) that exhibit inefficient pr-M cleavage (15). …”

Section: Resultsmentioning

confidence: 62%

“…Assignments for dISFs varied between insect only and vector borne, with those phylogenetically related to Lammi virus (LAMV) being assigned to the insect-only group, and those related to Barkedji virus (BJV) assigned to the vector-borne group. Bamaga virus (BgV), another recently discovered Australian flavivirus with limited replication in vertebrates, grouped closely with VIFs, consistent with its phylogenetic position (23). It was noteworthy that the flaviviruses with no known vector generally grouped closely with vector-borne viruses, with the exception of the highly divergent Tamana bat virus sequence, which was predicted to be associated only with a vertebrate host in this analysis.…”

Section: Resultsmentioning

confidence: 78%

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A New Clade of Insect-Specific Flaviviruses from Australian Anopheles Mosquitoes Displays Species-Specific Host Restriction

Colmant

Hobson‐Peters

Bielefeldt‐Ohmann

et al. 2017

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Flaviviruses like dengue, Zika, or West Nile virus infect millions of people each year and are transmitted to humans via infected-mosquito bites. A subset of flaviviruses can only replicate in the mosquito host, and recent studies have shown that some can interfere with pathogenic flaviviruses in mosquitoes and limit the replication and transmission of the latter. The insect-specific flaviviruses (ISFs) reported here form a new Anopheles mosquito-associated clade separate from the Aedes- and Culex-associated ISF clades. The identification of distinct clades for each mosquito genus provides new insights into the evolution and ecology of flaviviruses. One of these viruses was shown to replicate in the midgut of the mosquito host and exhibit the most specialized host restriction reported to date for ISFs. Understanding this unprecedented host restriction in ISFs could help identify the mechanisms involved in the evolution of flaviviruses and their emergence as mosquito-borne pathogens.

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Section: Resultsmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 78%

A New Clade of Insect-Specific Flaviviruses from Australian Anopheles Mosquitoes Displays Species-Specific Host Restriction

Colmant

Hobson‐Peters

Bielefeldt‐Ohmann

et al. 2017

mSphere

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“…We have previously shown that BgV replication could be detected in OK, HEK293 and BHK cells but not in Vero, DF-1, or RK-13 cells [11]. BgV replication was assessed in a wider range of insect and vertebrate cell lines at 28˚C or 37˚C, including in cell lines used in our previous study, as shown in Table 1.…”

Section: Bgv Is Host-restricted In Some Vertebrate Cells In Vitromentioning

confidence: 99%

“…As part of our ongoing efforts to characterise flavivirus host-restriction, this study aimed to investigate Bamaga virus attenuation and the mechanisms involved. Bamaga virus (BgV) was recently isolated from archival mosquito samples of the Culex sitiens subgroup collected in 2001 and 2004 from Cape York, Far North Queensland, Australia [11] and found to be phylogenetically most closely related to Edge Hill virus and other members of the yellow fever group. Despite this close genetic relationship, initial in vitro characterisation showed that BgV displayed a restricted host range, as it was only able to replicate efficiently in a subset of vertebrate cell lines, and displayed a host-restricted phenotype in CD1 mice [11].…”

Section: Introductionmentioning

confidence: 99%

“…Bamaga virus (BgV) was recently isolated from archival mosquito samples of the Culex sitiens subgroup collected in 2001 and 2004 from Cape York, Far North Queensland, Australia [11] and found to be phylogenetically most closely related to Edge Hill virus and other members of the yellow fever group. Despite this close genetic relationship, initial in vitro characterisation showed that BgV displayed a restricted host range, as it was only able to replicate efficiently in a subset of vertebrate cell lines, and displayed a host-restricted phenotype in CD1 mice [11]. In an effort to classify BgV, its genome sequence was analysed for nucleotide composition and dinucleotide usage bias, which demonstrated that this virus most likely alternates between arthropod vectors and vertebrate hosts [12].…”

Section: Introductionmentioning

confidence: 99%

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NS4/5 mutations enhance flavivirus Bamaga virus infectivity and pathogenicity in vitro and in vivo

et al. 2020

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Flaviviruses such as yellow fever, dengue or Zika viruses are responsible for significant human and veterinary diseases worldwide. These viruses contain an RNA genome, prone to mutations, which enhances their potential to emerge as pathogens. Bamaga virus (BgV) is a mosquito-borne flavivirus in the yellow fever virus group that we have previously shown to be host-restricted in vertebrates and horizontally transmissible by Culex mosquitoes. Here, we aimed to characterise BgV host-restriction and to investigate the mechanisms involved. We showed that BgV could not replicate in a wide range of vertebrate cell lines and animal species. We determined that the mechanisms involved in BgV host-restriction were independent of the type-1 interferon response and RNAse L activity. Using a BgV infectious clone and two chimeric viruses generated as hybrids between BgV and West Nile virus, we demonstrated that BgV host-restriction occurred post-cell entry. Notably, BgV host-restriction was shown to be temperature-dependent, as BgV replicated in all vertebrate cell lines at 34˚C but only in a subset at 37˚C. Serial passaging of BgV in Vero cells resulted in adaptive mutants capable of efficient replication at 37˚C. The identified mutations resulted in amino acid substitutions in NS4A-S124F, NS4B-N244K and NS5-G2C, all occurring close to a viral protease cleavage site (NS4A/2K and NS4B/NS5). These mutations were reverse engineered into infectious clones of BgV, which revealed that NS4B-N244K and NS5-G2C were sufficient to restore BgV replication in vertebrate cells at 37˚C, while NS4A-S124F further increased replication efficiency. When these mutant viruses were injected into immunocompetent mice, alongside BgV and West Nile virus chimeras, infection and neurovirulence were enhanced as determined by clinical scores, seroconversion, microneutralisation, viremia, histopathology and immunohistochemistry, confirming the involvement of these residues in the attenuation of BgV. Our studies identify a new mechanism of host-restriction and attenuation of a mosquito-borne flavivirus.

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The discovery and global distribution of novel mosquito‐associated viruses in the last decade (2007‐2017)

Atoni

Zhao

Karungu

et al. 2019

Reviews in Medical Virology

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Summary In the last decade, virus hunting and discovery has gained pace. This achievement has been driven by three major factors: (a) advancements in sequencing technologies, (b) scaled‐up routine arbovirus surveillance strategies, and (c) the “hunt” for emerging pathogens and novel viruses. Many novel viruses have been discovered from a myriad of hosts, vectors, and environmental samples. To help promote understanding of the global diversity and distribution of mosquito‐associated viruses and facilitate future studies, we review mosquito‐associated viruses discovered between years 2007 and 2017, across the world. In the analyzed period, novel mosquito‐associated viruses belonging to 25 families and a general group of unclassified viruses were categorized. The top three discovered novel mosquito‐associated viruses belonged to families Flaviviridae (n=32), Rhabdoviridae (n=16), and Peribunyaviridae (n=14). Also, 67 unclassified viruses were reported. Majority of these novel viruses were identified from Culex spp, Anopheles spp, Aedes spp, and Mansonia spp mosquitoes, respectively. Notably, the number of these discovered novels is not representative of intercontinental virus diversity but rather is influenced by the number of studies done in the study period. Some of these newly discovered mosquito‐associated viruses have medical significance, either directly or indirectly. For instance, in the study period, 14 novel mosquito‐borne viruses that infect mammalian cells in vitro were reported. These viruses pose a danger to the global health security on emerging viral diseases. On the other hand, some of the newly discovered insect specific viruses described herein have potential application as future biocontrol and vaccine agents against known pathogenic arboviruses. Overall, this review outlines the crucial role played by mosquitoes as viral vectors in the global virosphere.

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A newly discovered flavivirus in the yellow fever virus group displays restricted replication in vertebrates

Cited by 27 publications

References 43 publications

A New Clade of Insect-Specific Flaviviruses from Australian Anopheles Mosquitoes Displays Species-Specific Host Restriction

A New Clade of Insect-Specific Flaviviruses from Australian Anopheles Mosquitoes Displays Species-Specific Host Restriction

NS4/5 mutations enhance flavivirus Bamaga virus infectivity and pathogenicity in vitro and in vivo

The discovery and global distribution of novel mosquito‐associated viruses in the last decade (2007‐2017)

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