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Article ; Online: Evidence that untranslated genomic sequences are key determinants of insect-specific flavivirus host restriction.

Tangudu, Chandra S / Hargett, Alissa M / Blitvich, Bradley J

2022 Volume 574, Page(s) 102–114

Abstract: Most flaviviruses cycle between arthropods and vertebrates. Others, such as Long Pine Key virus (LPKV), are insect-specific. We investigated whether untranslated sequences in the genome of LPKV are critical determinants of its host restriction. A ... ...

Abstract	Most flaviviruses cycle between arthropods and vertebrates. Others, such as Long Pine Key virus (LPKV), are insect-specific. We investigated whether untranslated sequences in the genome of LPKV are critical determinants of its host restriction. A chimeric virus was created by inserting the entire 5' and 3' untranslated regions and capsid gene of LPKV into the genetic backbone of Zika virus (ZIKV). The virus replicated in mosquito cells, but not vertebrate cells. Three additional chimeras were created by exchanging specific regions in the 5' and 3' untranslated regions of ZIKV with the corresponding regions of LPKV. A chimera that contained stem loop A (the viral promoter) of LPKV in the genetic background of ZIKV produced virus that replicated in both mosquito and vertebrate cells. These data suggest that the ZIKV NS5 polymerase recognizes the LPKV promoter and that untranslated genomic elements, other than SLA, are key determinants of insect-specific flavivirus host-specificity.
MeSH term(s)	3' Untranslated Regions ; Animals ; Culicidae ; Flavivirus/genetics ; Genomics ; RNA, Viral/genetics ; Virus Replication ; Zika Virus/genetics ; Zika Virus Infection
Chemical Substances	3' Untranslated Regions ; RNA, Viral
Language	English
Publishing date	2022-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2022.07.013
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Article: Mosquito immune cells enhance dengue and Zika virus dissemination in

Hall, David R / Johnson, Rebecca M / Kwon, Hyeogsun / Ferdous, Zannatul / Laredo-Tiscareño, S Viridiana / Blitvich, Bradley J / Brackney, Doug E / Smith, Ryan C

bioRxiv : the preprint server for biology

2024

Abstract: Mosquito-borne viruses cause more than 400 million annual infections and place over half of the world's population at risk. Despite this importance, the mechanisms by which arboviruses infect the mosquito host and disseminate to tissues required for ... ...

Abstract	Mosquito-borne viruses cause more than 400 million annual infections and place over half of the world's population at risk. Despite this importance, the mechanisms by which arboviruses infect the mosquito host and disseminate to tissues required for transmission are not well understood. Here, we provide evidence that mosquito immune cells, known as hemocytes, play an integral role in the dissemination of dengue virus (DENV) and Zika virus (ZIKV) in the mosquito
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.03.587950
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Article ; Online: Arboviruses: Molecular Biology, Evolution and Control. Nikos Vasilakis and Duane J. Gubler.

Blitvich, Bradley

The American journal of tropical medicine and hygiene

2019 Volume 95, Issue 2, Page(s) 488–489

Language	English
Publishing date	2019-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.16-0281
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Article ; Online: Production of a chimeric flavivirus that contains the major structural glycoprotein genes of T'Ho virus in the genetic background of Zika virus.

Tangudu, Chandra S / Hargett, Alissa M / Mitrisin, Brooke C / Laredo-Tiscareño, S Viridiana / Blitvich, Bradley J

Virology journal

2023 Volume 20, Issue 1, Page(s) 197

Abstract: T'Ho virus is a poorly characterized orthoflavivirus most closely related to Rocio virus and Ilheus virus, two orthoflaviviruses associated with human disease, suggesting that T'Ho virus could also be a human pathogen. The genome of T'Ho virus has been ... ...

Abstract	T'Ho virus is a poorly characterized orthoflavivirus most closely related to Rocio virus and Ilheus virus, two orthoflaviviruses associated with human disease, suggesting that T'Ho virus could also be a human pathogen. The genome of T'Ho virus has been sequenced but an isolate has never been recovered, impeding its phenotypic characterization. In an attempt to generate recombinant T'Ho virus, the entire viral genome was synthesized as three overlapping DNA fragments, joined by Gibson assembly, and transfected into mosquito cells. Several cell culture passages were performed, but virus was not recovered. Subsequent experiments focused on the development of a chimeric orthoflavivirus that contains the premembrane and envelope protein genes of T'Ho virus in the genetic background of Zika virus. The chimeric virus replicated in mosquito (C6/36) and vertebrate (Vero) cells, demonstrating that the major structural glycoproteins of T'Ho virus permit entry into both cell types. The chimeric virus produced plaques in Vero cells that were significantly smaller than those produced by Zika virus. The chimeric virus can potentially be used as a surrogate diagnostic reagent in place of T'Ho virus in plaque reduction neutralization tests, allowing T'Ho virus to be considered in the differential diagnosis.
MeSH term(s)	Chlorocebus aethiops ; Humans ; Animals ; Zika Virus/genetics ; Flavivirus/genetics ; Vero Cells ; Genetic Background ; Culicidae ; Zika Virus Infection
Chemical Substances	structural-GP protein, Bos taurus
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/s12985-023-02172-2
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Article ; Online: Biology and Transmission Dynamics of Aedes flavivirus.

Peinado, Stephen A / Aliota, Matthew T / Blitvich, Bradley J / Bartholomay, Lyric C

Journal of medical entomology

2022 Volume 59, Issue 2, Page(s) 659–666

Abstract: Aedes albopictus (Skuse) and Aedes aegypti (Linnaeus) (Diptera: Culicidae) mosquitoes transmit pathogenic arthropod-borne viruses, including dengue, chikungunya, and Zika viruses, with significant global health consequences. Both Ae. albopictus and Ae. ... ...

Abstract	Aedes albopictus (Skuse) and Aedes aegypti (Linnaeus) (Diptera: Culicidae) mosquitoes transmit pathogenic arthropod-borne viruses, including dengue, chikungunya, and Zika viruses, with significant global health consequences. Both Ae. albopictus and Ae. aegypti also are susceptible to Aedes flavivirus (AEFV), an insect-specific flavivirus (ISF) first isolated in Japan from Ae. albopictus and Ae. flavopictus. ISFs infect only insect hosts and evidence suggests that they are maintained by vertical transmission. In some cases, ISFs interfere with pathogenic flavivirus infection, and may have potential use in disease control. We explored the host range of AEFV in 4 genera of mosquitoes after intrathoracic injection and observed greater than 95% prevalence in the species of Aedes and Toxorhynchites tested. Anopheles and Culex species were less permissive to infection. Vertical transmission studies revealed 100% transovarial transmission and a filial infection rate of 100% for AEFV in a persistently-infected colony of Ae. albopictus. Horizontal transmission potential was assessed for adult and larval mosquitoes following per os exposures and in venereal transmission experiments. No mosquitoes tested positive for AEFV infection after blood feeding, and infection with AEFV after sucrose feeding was rare. Similarly, 2% of adult mosquitoes tested positive for AEFV after feeding on infected cells in culture as larvae. Venereal transmission of AEFV was most frequently observed from infected males to uninfected females as compared with transmission from infected females to uninfected males. These results reveal new information on the infection potential of AEFV in mosquitoes and expand our understanding of both vertical and horizontal transmission of ISFs.
MeSH term(s)	Aedes ; Animals ; Biology ; Female ; Flavivirus ; Insecta ; Larva ; Male ; Mosquito Vectors ; Zika Virus ; Zika Virus Infection
Language	English
Publishing date	2022-01-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	410635-0
ISSN	1938-2928 ; 0022-2585
ISSN (online)	1938-2928
ISSN	0022-2585
DOI	10.1093/jme/tjab197
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Article ; Online: Continued Need for Comprehensive Genetic and Phenotypic Characterization of Viruses: Benefits of Complementing Sequence Analyses with Functional Determinations.

Brault, Aaron C / Blitvich, Bradley J

The American journal of tropical medicine and hygiene

2018 Volume 98, Issue 5, Page(s) 1213

MeSH term(s)	Orthobunyavirus ; Phylogeny ; RNA Viruses ; Sequence Analysis ; Serogroup
Language	English
Publishing date	2018-03-15
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.18-0128
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Article ; Online: A Review of Flaviviruses that Have No Known Arthropod Vector.

Blitvich, Bradley J / Firth, Andrew E

Viruses

2017 Volume 9, Issue 6

Abstract: Most viruses in the ... ...

Abstract	Most viruses in the genus
MeSH term(s)	Animals ; Arthropod Vectors ; Chiroptera/virology ; Disease Transmission, Infectious ; Flaviviridae Infections/transmission ; Flaviviridae Infections/veterinary ; Flavivirus/isolation & purification ; Rodentia/virology
Language	English
Publishing date	2017-06-21
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v9060154
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Article ; Online: Isolation of a novel rhabdovirus and detection of multiple novel viral sequences in Culex species mosquitoes in the United States.

Tangudu, Chandra S / Hargett, Alissa M / Laredo-Tiscareño, S Viridiana / Smith, Ryan C / Blitvich, Bradley J

Archives of virology

2022 Volume 167, Issue 12, Page(s) 2577–2590

Abstract: To increase our understanding of the diversity of the mosquito virome, 6956 mosquitoes of five species (Culex erraticus, Culex pipiens, Culex restuans, Culex tarsalis, and Culex territans) collected in Iowa in the United States in 2017 and 2020 were ... ...

Abstract	To increase our understanding of the diversity of the mosquito virome, 6956 mosquitoes of five species (Culex erraticus, Culex pipiens, Culex restuans, Culex tarsalis, and Culex territans) collected in Iowa in the United States in 2017 and 2020 were assayed for novel viruses by performing polyethylene glycol precipitation, virus isolation in cell culture, and unbiased high-throughput sequencing. A novel virus, provisionally named "Walnut Creek virus", was isolated from Cx. tarsalis, and its genomic sequence and organization are characteristic of viruses in the genus Hapavirus (family Rhabdoviridae). Replication of Walnut Creek virus occurred in avian, mammalian, and mosquito, but not tick, cell lines. A novel virus was also isolated from Cx. restuans, and partial genome sequencing revealed that it is distantly related to an unclassified virus of the genus Phytoreovirus (family Sedoreoviridae). Two recognized viruses were also isolated: Culex Y virus (family Birnaviridae) and Houston virus (family Mesoniviridae). We also identified sequences of eight novel viruses from six families (Amalgaviridae, Birnaviridae, Partitiviridae, Sedoreoviridae, Tombusviridae, and Totiviridae), two viruses that do not belong to any established families, and many previously recognized viruses. In summary, we provide evidence of multiple novel and recognized viruses in Culex spp. mosquitoes in the United States.
Language	English
Publishing date	2022-09-03
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-022-05586-5
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Article ; Online: The host range restriction of bat-associated no-known-vector flaviviruses occurs post-entry.

Charles, Jermilia / Tangudu, Chandra S / Nunez-Avellaneda, Daniel / Brault, Aaron C / Blitvich, Bradley J

The Journal of general virology

2021 Volume 102, Issue 9

Abstract: Most flaviviruses are transmitted horizontally between vertebrate hosts by haematophagous arthropods. Others exhibit host ranges restricted to vertebrates or arthropods. Vertebrate-specific flaviviruses are commonly referred to as no-known-vector (NKV) ... ...

Abstract	Most flaviviruses are transmitted horizontally between vertebrate hosts by haematophagous arthropods. Others exhibit host ranges restricted to vertebrates or arthropods. Vertebrate-specific flaviviruses are commonly referred to as no-known-vector (NKV) flaviviruses and can be separated into bat- and rodent-associated NKV flaviviruses. Rio Bravo virus (RBV) is one of eight recognized bat-associated NKV (B-NKV) flaviviruses. Studies designed to identify the genetic determinants that condition the host range restriction of B-NKV flaviviruses have never been performed. To investigate whether the host range restriction occurs at the level of attachment or entry, chimeric flaviviruses were created by inserting the pre-membrane and envelope protein genes of RBV into the genetic backbones of yellow fever virus (YFV) and Zika virus (ZIKV), two mosquito-borne flaviviruses associated with human disease. The chimeric viruses infected both vertebrate and mosquito cells. In vertebrate cells, all viruses produced similar mean peak titres, but the chimeric viruses grew more slowly than their parental viruses during early infection. In mosquito cells, the chimeric virus of YFV and RBV grew more slowly than YFV at early post-inoculation time points, but reached a similar mean peak titre. In contrast, the chimeric virus of ZIKV and RBV produced a mean peak titre that was approximately 10-fold lower than ZIKV. The chimeric virus of YFV and RBV produced an intermediate plaque phenotype, while the chimeric virus of ZIKV and RBV produced smaller plaques than both parental viruses. To conclude, we provide evidence that the structural glycoproteins of RBV permit entry into both mosquito and vertebrate cells, indicating that the host range restriction of B-NKV flaviviruses is mediated by a post-attachment/entry event.
MeSH term(s)	Animals ; Cell Line ; Chiroptera/virology ; Flavivirus/genetics ; Flavivirus/physiology ; Gene Transfer Techniques ; Genes, Viral ; Genes, env ; Genome, Viral ; Host Specificity ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/physiology ; Viral Load ; Viral Plaque Assay ; Virus Attachment ; Virus Internalization ; Virus Replication ; Yellow fever virus/genetics ; Yellow fever virus/physiology ; Zika Virus/genetics ; Zika Virus/physiology
Chemical Substances	Viral Envelope Proteins ; prM protein, Flavivirus
Language	English
Publishing date	2021-09-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001647
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Article ; Online: Complete nucleotide sequences of the large RNA genome segments of Main Drain and Northway viruses (family Peribunyaviridae).

Charles, Jermilia / Tangudu, Chandra S / Blitvich, Bradley J

Archives of virology

2018 Volume 163, Issue 8, Page(s) 2253–2255

Abstract: The large RNA genome segments of Main Drain virus (MDV) and Northway virus (NORV) were fully sequenced and shown to consist of 6860 and 6875 nucleotides, respectively. Sequence alignments revealed that the large RNA segment of MDV is most closely related ...

Abstract	The large RNA genome segments of Main Drain virus (MDV) and Northway virus (NORV) were fully sequenced and shown to consist of 6860 and 6875 nucleotides, respectively. Sequence alignments revealed that the large RNA segment of MDV is most closely related to the corresponding region of NORV, with 76.8% nucleotide sequence identity, and the large RNA segment of NORV is most closely related to the corresponding region of Maguari virus, with 79.1% identity.
MeSH term(s)	Animals ; Base Sequence ; Ceratopogonidae/virology ; Culicidae/virology ; Genome, Viral ; Orthobunyavirus/classification ; Orthobunyavirus/genetics ; Orthobunyavirus/isolation & purification ; Phylogeny ; RNA, Viral/genetics ; Viral Proteins/genetics
Chemical Substances	RNA, Viral ; Viral Proteins
Language	English
Publishing date	2018-04-03
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-018-3826-6
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