Serological evidence for the co‐circulation of two lineages of influenza D viruses in equine populations of the Midwest United States

Nedland, Hunter; Wollman, Jared W; Sreenivasan, Chithra; Quast, Megan; Singrey, Aaron; Fawcett, L.; Christopher‐Hennings, Jane; Nelson, E.; Kaushik, Radhey S.; Wang, Dan Dan; Feng, Liang

doi:10.1111/zph.12423

Cited by 77 publications

(83 citation statements)

References 13 publications

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“…Further epidemiological studies revealed that IDVs circulate in cattle in many countries including the USA (2–4), Mexico (5), China (6), Japan (7, 8), France (9), Italy (10), Ireland (11), Luxembourg (12), and African countries (13). Furthermore, serological studies showed that IDV antibodies are found in pigs (14), sheep (15, 16), goats (15, 16), dromedary camels (13, 17), horses (18), and humans (19). These findings imply that IDVs are globally distributed in several animal hosts.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a Reverse Genetics System for Influenza D Virus

Ishida

Murakami

Kamiki

et al. 2019

Preprint

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250 words 15 Text 4,170 words 16 2 ABSTRACT Influenza D virus (IDV) was initially isolated in the USA in 2011. IDV is 17distributed worldwide and is one of the causative agents of bovine respiratory disease 18 complex (BRDC), which exhibits high morbidity and mortality in feedlot cattle. 19 Molecular mechanisms of IDV pathogenicity are still unknown. Reverse genetics 20 systems are vital tools not only for studying the biology of viruses, but also for use in 21 applications such as recombinant vaccine viruses. Here, we report the establishment of a 22 plasmid-based reverse genetics system for IDV. We first verified that the 3′-terminal 23 nucleotide of each 7-segmented genomic RNA contained uracil in contrary to the 24 previous report, and were then able to successfully generate recombinant IDV by 25 co-transfecting 7 plasmids containing these genomic RNAs along with 4 plasmids 26 expressing polymerase proteins and NP into HRT-18G cells. The recombinant virus had 27 a growth deficit compared to the wild-type virus, and we determined the reason for this 28 growth difference by examining the genomic RNA content of the viral particles. We 29 found that recombinant virus incorporated an unbalanced ratio of viral RNA segments 30 into particles as compared to the wild-type virus, and thus we adjusted the amount of 31 each plasmid used in transfection to obtain recombinant virus with the same replicative 32 capacity as wild-type virus. Our work here in establishing a reverse genetics system for 33 IDV will have a broad range of applications, including uses in studies focused on better 34 understanding IDV replication and pathogenicity as well as those contributing to the 35 development of BRDC countermeasures. 36 37 IMPORTANCE Bovine respiratory disease complex (BRDC) exhibits high mortality 38 and morbidity in cattle, causing economic losses worldwide. Influenza D virus (IDV) is 39 considered to be a causative agent of BRDC. Here, we developed a reverse genetics 40 3 system that allows for the generation of IDV from cloned cDNAs, and the introduction 41 of mutations into the IDV genome. This reverse genetics system will become a 42 powerful tool for use in studies related to understanding the molecular mechanisms of 43 viral replication and pathogenicity, and will also lead to the development of new 44 countermeasures against BRDC. 45 46 KEYWORD bovine respiratory disease complex, influenza D virus, mutant, 47 recombinant virus, reverse genetics, transfection 48 49 50 Influenza D virus (IDV), a member of the family Orthomyxoviridae, was first isolated 52 from pigs with respiratory illness in Oklahoma, USA, in 2011 (1, 2). Epidemiological 53 analyses revealed that cattle are the main host of the virus, due to their high 54 seroprevalence for IDV (2, 3). Further epidemiological studies revealed that IDVs 55 circulate in cattle in many countries including the USA (2-4), Mexico (5), China (6), 56 Japan (7, 8), France (9), Italy (10), Ireland (11), Luxembourg (12), and African 57 countries (13). Furthermore, serolo...

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Section: Introductionmentioning

confidence: 99%

Establishment of a Reverse Genetics System for Influenza D Virus

Ishida

Murakami

Kamiki

et al. 2019

Preprint

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“…Two lineages of IDVs are primarily responsible for current IDV global infections (1,3,13). Furthermore, these two distinct lineages of IDVs can also coinfect the same animals (3,19). To develop an IDV vaccine that could prevent infection from both lineages of IDV, we designed and constructed an IDV HEF consensus gene (ConD-HEF)-based vaccine, FluD-Vax.…”

Section: Resultsmentioning

confidence: 99%

“…However, subsequently epidemiological data suggest cattle are the primary reservoir (1,5,7,8). In addition to swine and cattle, IDV infections have been reported in goats, sheep, equines, buffalos, and camels (2,5,9,10). IDV has also been shown to infect ferrets (4) and guinea pigs (11,12) in experimental settings.…”

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confidence: 99%

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A DNA Vaccine Expressing Consensus Hemagglutinin-Esterase Fusion Protein Protected Guinea Pigs from Infection by Two Lineages of Influenza D Virus

Wan

Kang

Sreenivasan

et al. 2018

J Virol

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Two lineages of influenza D virus (IDV) have been found to infect cattle and promote bovine respiratory disease complex, one of the most commonly diagnosed causes of morbidity and mortality within the cattle industry. Furthermore, IDV can infect other economically important domestic livestock, including pigs, and has the potential to infect humans, which necessitates the need for an efficacious vaccine. In this study, we designed a DNA vaccine expressing consensus hemagglutinin-esterase fusion (HEF) protein (FluD-Vax) and tested its protective efficacy against two lineages of IDV (D/OK and D/660) in guinea pigs. Animals that received FluD-Vax ( = 12) developed appreciable titers of neutralizing antibodies against IDV lineage representatives, D/OK and D/660. Importantly, vaccinated animals were protected against intranasal challenge with IDV [3 × 10 50% tissue culture infective dose(s) (TCID)] D/OK ( = 6) or D/600 ( = 6), based on the absence of viral RNA in necropsied tissues (5 and 7 days postchallenge) using quantitative reverse transcription-PCR and hybridization. In contrast, animals that received a sham DNA vaccine ( = 12) had no detectable neutralizing antibodies against IDV, and viral RNA was readily detectable in respiratory tract tissues after intranasal challenge (3 × 10 TCID) with IDV D/OK ( = 6) or D/660 ( = 6). Using a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay, we found that IDV D/OK and D/600 infections induced apoptosis in epithelial cells lining alveoli and bronchioles, as well as nonepithelial cells in lung tissues. Our results demonstrate for the first time that the consensus IDV HEF DNA vaccine can elicit complete protection against infection from two lineages of IDV in the guinea pig model. Influenza D virus (IDV) infection has been associated with bovine respiratory disease complex, one of the most devastating diseases of the cattle population. Moreover, with broad host range and high environmental stability, IDV has the potential to further gain virulence or even infect humans. An efficacious vaccine is needed to prevent infection and stop potential cross-species transmission. In this study, we designed a DNA vaccine encoding the consensus hemagglutinin-esterase fusion (HEF) protein of two lineages of IDV (D/OK and D/660) and tested its efficacy in a guinea pig model. Our results showed that the consensus DNA vaccine elicited high-titer neutralizing antibodies and achieved sterilizing protection against two lineage-representative IDV intranasal infections. To our knowledge, this is the first study showing that a DNA vaccine expressing consensus HEF is efficacious in preventing different lineages of IDV infections.

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“…Because of the high seroprevalence, cattle is the proposed natural reservoir of IDV, in which IDV causes mild respiratory disease symptoms (11). In addition to cattle, IDV-specific antibodies have been detected in swine, feral swine, equine, ovine, caprine and camelid species, suggesting a broad host tropism for IDV (3, 4, 9, 12, 13). However, the most striking observation is the detection of IDV-directed antibodies among humans with occupational exposure to livestock (14).…”

Section: Introductionmentioning

confidence: 99%

Determining the replication kinetics and cellular tropism of the ruminant-associated Influenza D virus on primary human airway epithelial cells

Holwerda

Laloli

Stuermer

et al. 2018

Preprint

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One-sentence summary of the conclusion 33 We show that the ruminant-associated Influenza D virus has direct transmission capability to 34 humans. 35 36 Abstract 37 Influenza viruses are notorious pathogens that frequently cross the species barrier with often 38 severe consequences for both animal and human health. In 2011, a novel member of the 39 Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of 40 diseased swine. Epidemiological surveys revealed that IDV is distributed worldwide among 41 livestock and that IDV-directed antibodies are detected in humans with occupational exposure 42 to livestock. To identify the transmission capability of IDV to humans, we determined the 43 viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of 44 humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny 45 virus release at different body temperatures. Intriguingly, the replication characteristics of 46 IDV revealed many similarities to the human-associated Influenza C virus, including the cell 47 tropism preference for ciliated cells. Collectively, these results might indicate why IDV-48 directed antibodies are detected among humans with occupational exposure to livestock. 49 50 51After the initial discovery of Influenza D virus (IDV) in 2011, among swine with Influenza-52 like symptoms, knowledge about this new genus in the family of Orthomyxoviridae is 53 increasing (1, 2). Epidemiological studies have shown that the virus has a worldwide 54 distribution, whereby at least two distinct genetic lineages are cocirculating and reassorting 55 (3-10). Because of the high seroprevalence, cattle is the proposed natural reservoir of IDV, in 56 which IDV causes mild respiratory disease symptoms (11). In addition to cattle, IDV-specific 57 antibodies have been detected in swine, feral swine, equine, ovine, caprine and camelid 58 species, suggesting a broad host tropism for IDV (3, 4, 9, 12, 13). However, the most striking 59 observation is the detection of IDV-directed antibodies among humans with occupational 60 exposure to livestock (14). 61There are several indicators that IDV has a zoonotic potential. For instance, the 62 utilization of the 9-O-acetyl-N-acetylneuraminic acid as a receptor determinant, that allows 63 the hemaglutinin esterase fusion (HEF) glycoprotein of IDV to bind the luminal surface of the 64 human respiratory epithelium (1). Interestingly, the utilization of this receptor is also 65 described for the closely related, human associated Influenza C virus (ICV) (15, 16). 66 Furthermore, the detection of IDV-directed antibodies among humans with occupational 67 exposure to livestock and the molecular detection of IDV in a nasopharyngeal wash of a field 68 worker with close contact to livestock indicates that cross species transmission occurs (14, 69 17). However, thus far, there is no indication of wide spread prevalence among the general 70 population although the virus has been detect...

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Serological evidence for the co‐circulation of two lineages of influenza D viruses in equine populations of the Midwest United States

Cited by 77 publications

References 13 publications

Establishment of a Reverse Genetics System for Influenza D Virus

Establishment of a Reverse Genetics System for Influenza D Virus

A DNA Vaccine Expressing Consensus Hemagglutinin-Esterase Fusion Protein Protected Guinea Pigs from Infection by Two Lineages of Influenza D Virus

Determining the replication kinetics and cellular tropism of the ruminant-associated Influenza D virus on primary human airway epithelial cells

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