Search Results (36)

Increased evidence suggests that cattle are the primary host of Influenza D virus (IDV) and may contribute to respiratory disease in this species. The aim of this study was to detect and characterise IDV in the Swedish cattle population using archived respiratory samples. This retrospective study comprised a collection of a total 1763 samples collected between 1 January 2021 and 30 June 2024. The samples were screened for IDV and other respiratory pathogens using real-time reverse transcription quantitative PCR (rRT-qPCR). Fifty-one IDV-positive samples were identified, with a mean cycle threshold (Ct) value of 27 (range: 15–37). Individual samples with a Ct value of <30 for IDV RNA were further analysed by deep sequencing. Phylogenetic analysis was performed by the maximum likelihood estimation method on the whole IDV genome sequence from 16 samples. The IDV strains collected in 2021 (n = 7) belonged to the D/OK clade, whereas samples from 2023 (n = 4) and 2024 (n = 5) consisted of reassortants between the D/OK and D/660 clades, for the PB2 gene. This study reports the first detection of IDV in Swedish cattle and the circulation of D/OK and reassortant D/OK-D/660 in this population. Full article

The bovine respiratory disease complex (BRD) is a multifactorial disease caused by various bacterial and viral pathogens. Using rapid pathogen detection techniques is helpful for tailoring therapeutic and preventive strategies in affected animals and herds. The objective of this study was to report the frequency of 10 pathogens by multiplex RT-qPCR on samples submitted for BRD diagnosis to a diagnostic laboratory (Biovet Inc., QC, Canada) in the Province of Quebec, Eastern Canada. From the 1st of January 2019 to the 31st of December 2023, a total of 1875 samples were analyzed. Most samples collected were individual samples (1547 of 1860 samples for which information was available (83.17%)), and the rest were from pooled samples of 2 (8.55%, n = 159) or ≥3 specimens (8.28%, n = 154). In 19.3% of the samples (n = 362), no pathogen was found, whereas 54.1% of samples had two or more different pathogens. Among the viruses, bovine coronavirus (BCV) was the most commonly found (27.5% of samples, n = 516), followed by bovine respiratory syncytial virus (BRSV) (17.7%, n = 332), whereas, for bacteria, Pasteurella multocida (50.1%, n = 940) and Mannheimia haemolytica (26.9%, n = 505) were the most common. The frequency of samples positive for Histophilus somni, Mycoplasmopsis bovis, influenza type D virus (IDV), bovine parainfluenza virus type 3 (BPI3V), bovine herpesvirus type 1 (BHV1), and bovine viral diarrhea virus (BVDV) was 22.6%, 22.4%, 4.6%, 4.3%, 2.7%, and 0.9%, respectively. In the multivariable Poisson regression model, the total number of pathogens increased with the number of animals in the pool, with an incidence risk ratio (IRR) of 1.15 (95% CI 1.02–1.29) and 1.32 (1.18–1.47) for 2 individuals in the pool and ≥3 individuals vs. individual samples, respectively. An increased number of pathogens were isolated in the winter season (IRR = 1.28 (95% CI 1.17–1.40)) compared to fall, and a lower number of pathogens were isolated in the summer compared to fall (IRR = 0.82 (95% CI 0.73–0.92)). These seasonal differences were mostly driven by the number of viruses isolated. This study gives interesting insights on the circulation of BRD pathogens in cattle from Eastern Canada. Full article

Influenza D virus (IDV) is a newly emerged zoonotic virus increasingly reported worldwide. Cattle are considered the main reservoir of IDV, although it was first isolated from pigs. IDV infects multiple animal species and contributes to the bovine respiratory disease complex (BRDC). To date, there has been no report on the presence and frequency of IDV among cattle herds in Pakistan. In this study, we collected nasal swabs from cattle and performed virological surveillance of IDV via qRT-PCR. Among 376 swab samples, IDV was detected in 9 samples (2.4%). Four dairy cattle farms were positive for IDV; two IDV-positive samples (two/nine, 22.2%) belonged to asymptomatic cattle, while seven IDV-positive samples (seven/nine, 77.8%) were from cattle showing respiratory clinical signs, including two with a recent history of abortion and mastitis. Partial sequences of the hemagglutinin–esterase-fusion gene of IDV were obtained from nine qRT-PCR-positive samples. Notably, all IDV strains in this study clustered within the D/OK lineages in phylogenetic analysis. A 98.8–99.6% genetic identity to its European and US counterparts indicates that the IDVs are closely related. The D/OK lineage of IDV was previously unreported in Pakistan. This is the first report of IDV in Pakistan. We confirmed that IDV is circulating among cattle herds in Pakistan. This study underscores the importance of virological surveillance to monitor the ecology of IDV for better animal and public health. The continued spread of IDV and its adaptation to various hosts necessitate further epidemiological studies. Full article

Background: Influenza D Virus (IDV) presents a possible threat to animal and human health, necessitating the development of effective vaccines. Although no human illness linked to IDV has been reported, the possibility of human susceptibility to infection remains uncertain. Hence, there is a need for an animal vaccine to be designed. Such a vaccine will contribute to preventing and controlling IDV outbreaks and developing effective countermeasures against this emerging pathogen. This study, therefore, aimed to design an mRNA vaccine construct against IDV using immunoinformatic methods and evaluate its potential efficacy. Methods: A comprehensive methodology involving epitope prediction, vaccine construction, and structural analysis was employed. Viral sequences from six continents were collected and analyzed. A total of 88 Hemagglutinin Esterase Fusion (HEF) sequences from IDV isolates were obtained, of which 76 were identified as antigenic. Different bioinformatics tools were used to identify preferred CTL, HTL, and B-cell epitopes. The epitopes underwent thorough analysis, and those that can induce a lasting immunological response were selected for the construction. Results: The vaccine prototype comprised nine epitopes, an adjuvant, MHC I-targeting domain (MITD), Kozaq, 3′ UTR, 5′ UTR, and specific linkers. The mRNA vaccine construct exhibited antigenicity, non-toxicity, and non-allergenicity, with favourable physicochemical properties. The secondary and tertiary structure analyses revealed a stable and accurate vaccine construct. Molecular docking simulations also demonstrated strong binding affinity with toll-like receptors. Conclusions: The study provides a promising framework for developing an effective mRNA vaccine against IDV, highlighting its potential for mitigating the global impact of this viral infection. Further experimental studies are needed to confirm the vaccine’s efficacy and safety. Full article

Influenza D virus (IDV) is the most recent addition to the Orthomyxoviridae family and cattle serve as the primary reservoir. IDV has been implicated in Bovine Respiratory Disease Complex (BRDC), and there is serological evidence of human infection of IDV. Evolutionary changes in the IDV genome have resulted in the expansion of genetic diversity and the emergence of multiple lineages that might expand the host tropism and potentially increase the pathogenicity to animals and humans. Therefore, there is an urgent need for automated, accurate and rapid typing tools for IDV lineage typing. Currently, IDV lineage typing is carried out using BLAST-based searches and alignment-based molecular phylogeny of the hemagglutinin-esterase fusion (HEF) gene sequences, and lineage is assigned to query sequences based on sequence similarity (BLAST search) and proximity to the reference lineages in the tree topology, respectively. To minimize human intervention and lineage typing time, we developed IDV Typer server, implementing alignment-free method based on return time distribution (RTD) of k-mers. Lineages are assigned using HEF gene sequences. The server performs with 100% sensitivity and specificity. The IDV Typer server is the first application of an RTD-based alignment-free method for typing animal viruses. Full article

The role of Influenza D virus (IDV) in bovine respiratory disease remains unclear. An in vivo experiment resulted in increased clinical signs, lesions, and pathogen replication in calves co-infected with IDV and Mycoplasma bovis (M. bovis), compared to single-infected calves. The present study aimed to elucidate the host–pathogen interactions and profile the kinetics of lipid mediators in the airways of these calves. Bronchoalveolar lavage (BAL) samples collected at 2 days post-infection (dpi) were used for proteomic analyses by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, lipidomic analyses were performed by LC-MS/MS on BAL samples collected at 2, 7 and 14 dpi. Whereas M. bovis induced the expression of proteins involved in fibrin formation, IDV co-infection counteracted this coagulation mechanism and downregulated other acute-phase response proteins, such as complement component 4 (C4) and plasminogen (PLG). The reduced inflammatory response against M. bovis likely resulted in increased M. bovis replication and delayed M. bovis clearance, which led to a significantly increased abundance of oxylipids in co-infected calves. The identified induced oxylipids mainly derived from arachidonic acid; were likely oxidized by COX-1, COX-2, and LOX-5; and peaked at 7 dpi. This paper presents the first characterization of BAL proteome and lipid mediator kinetics in response to IDV and M. bovis infection in cattle and raises hypotheses regarding how IDV acts as a co-pathogen in bovine respiratory disease. Full article

Influenza D virus (IDV) is a novel orthomyxovirus initially isolated from pigs exhibiting influenza-like disease in the USA. Since then, IDV has been detected worldwide in several host species, including livestock animals, whilst specific antibodies have been identified in humans, raising concerns about interspecies transmission and zoonotic risks. Few data regarding the seroprevalence of IDV in small ruminants have been available to date. In this study, we assessed the prevalence of antibodies against IDV in ovine serum samples in Sicily, Southern Italy. Six hundred serum samples, collected from dairy sheep herds located in Sicily in 2022, were tested by haemagglutination inhibition (HI) and virus neutralization (VN) assays using reference strains, D/660 and D/OK, representative of two distinct IDV lineages circulating in Italy. Out of 600 tested samples, 168 (28.0%) tested positive to either IDV strain D/660 or D/OK or to both by HI whilst 378 (63.0%) tested positive to either IDV strain D/660 or D/OK or to both by VN. Overall, our findings demonstrate that IDV circulates in ovine dairy herds in Sicily. Since IDV seems to have a broad host range and it has zoonotic potential, it is important to collect epidemiological information on susceptible species. Full article

Influenza D virus (IDV) can infect various livestock animals, such as cattle, swine, and small ruminants, and was shown to have zoonotic potential. Therefore, it is important to identify viral factors involved in the broad host tropism and identify potential antiviral compounds that can inhibit IDV infection. Recombinant reporter viruses provide powerful tools for studying viral infections and antiviral drug discovery. Here we present the generation of a fluorescent reporter IDV using our previously established reverse genetic system for IDV. The mNeonGreen (mNG) fluorescent reporter gene was incorporated into the IDV non-structural gene segment as a fusion protein with the viral NS1 or NS2 proteins, or as a separate protein flanked by two autoproteolytic cleavage sites. We demonstrate that only recombinant reporter viruses expressing mNG as an additional separate protein or as an N-terminal fusion protein with NS1 could be rescued, albeit attenuated, compared to the parental reverse genetic clone. Serial passaging experiments demonstrated that the mNG gene is stably integrated for up to three passages, after which internal deletions accumulate. We conducted a proof-of-principle antiviral screening with the established fluorescent reporter viruses and identified two compounds influencing IDV infection. These results demonstrate that the newly established recombinant IDV reporter virus can be applied for antiviral drug discovery and monitoring viral replication, adding a new molecular tool for investigating IDV. Full article

Bovine viral diarrhea virus (BVDV) induces immunosuppression and thymus depletion in calves. This study explores the impact of prior BVDV-2 exposure on the subsequent immune response to influenza D virus (IDV). Twenty 3-week-old calves were divided into four groups. Calves in G1 and G3 were mock-treated on day 0, while calves in G2 and G4 received BVDV. Calves in G1 (mock) and G2 (BVDV) were necropsied on day 13 post-infection. IDV was inoculated on day 21 in G3 calves (mock + IDV) and G4 (BVDV + IDV) and necropsy was conducted on day 42. Pre-exposed BVDV calves exhibited prolonged and increased IDV shedding in nasal secretions. An approximate 50% reduction in the thymus was observed in acutely infected BVDV calves (G2) compared to controls (G1). On day 42, thymus depletion was observed in two calves in G4, while three had normal weight. BVDV-2-exposed calves had impaired CD8 T cell proliferation after IDV recall stimulation, and the α/β T cell impairment was particularly evident in those with persistent thymic atrophy. Conversely, no difference in antibody levels against IDV was noted. BVDV-induced thymus depletion varied from transient to persistent. Persistent thymus atrophy was correlated with weaker T cell proliferation, suggesting correlation between persistent thymus atrophy and impaired T cell immune response to subsequent infections. Full article

Influenza D virus (IDV) infections have been observed in animals worldwide, confirmed through both serological and molecular tests, as well as virus isolation. IDV possesses unique properties that distinguish it from other influenza viruses, primarily attributed to the hemagglutinin-esterase fusion (HEF) surface glycoprotein, which determines the virus’ tropism and wide host range. Cattle are postulated to be the reservoir of IDV, and the virus is identified as one of the causative agents of bovine respiratory disease (BRD) syndrome. Animals associated with humans and susceptible to IDV infection include camels, pigs, small ruminants, and horses. Notably, high seroprevalence towards IDV, apart from cattle, is also observed in camels, potentially constituting a reservoir of the virus. Among wild and captive animals, IDV infections have been confirmed in feral pigs, wild boars, deer, hedgehogs, giraffes, wildebeests, kangaroos, wallabies, and llamas. The transmission potential and host range of IDV may contribute to future viral differentiation. It has been confirmed that influenza D may pose a threat to humans as a zoonosis, with seroprevalence noted in people with professional contact with cattle. Full article

Influenza D virus (IDV) belongs to the Orthomyxoviridae family, which also include the influenza A, B and C virus genera. IDV was first detected and isolated in 2011 in the United States from pigs with respiratory illness. IDV circulates in mammals, including pigs, cattle, camelids, horses and small ruminants. Despite the broad host range, cattle are thought to be the natural reservoir of IDV. This virus plays a role as a causative agent of the bovine respiratory disease complex (BRDC). IDV has been identified in North America, Europe, Asia and Africa. However, there has been no information on the presence of IDV in the Republic of Korea (ROK). In this study, we investigated the presence of viral RNA and seroprevalence to IDV among cattle and pigs in the ROK in 2022. Viral RNA was surveyed by the collection and testing of 999 cattle and 2391 pig nasal swabs and lung tissues using a real-time RT-PCR assay. IDV seroprevalence was investigated by testing 742 cattle and 1627 pig sera using a hemagglutination inhibition (HI) assay. The viral RNA positive rate was 1.4% in cattle, but no viral RNA was detected in pigs. Phylogenetic analysis of the hemagglutinin-esterase-fusion (HEF) gene was further conducted for a selection of samples. All sequences belonged to the D/Yamagata/2019 lineage. The seropositivity rates were 54.7% in cattle and 1.4% in pigs. The geometric mean of the antibody titer (GMT) was 68.3 in cattle and 48.5 in pigs. This is the first report on the detection of viral RNA and antibodies to IDV in the ROK. Full article

Influenza D virus (IDV) has been detected in bovine respiratory disease (BRD) outbreaks, and experimental studies demonstrated this virus’s capacity to cause lesions in the respiratory tract. In addition, IDV-specific antibodies were detected in human sera, which indicated that this virus plays a potential zoonotic role. The present study aimed to extend our knowledge about the epidemiologic situation of IDV in Swedish dairy farms, using bulk tank milk (BTM) samples for the detection of IDV antibodies. A total of 461 and 338 BTM samples collected during 2019 and 2020, respectively, were analyzed with an in-house indirect ELISA. In total, 147 (32%) and 135 (40%) samples were IDV-antibody-positive in 2019 and 2020, respectively. Overall, 2/125 (2%), 11/157 (7%) and 269/517 (52%) of the samples were IDV-antibody-positive in the northern, middle and southern regions of Sweden. The highest proportion of positive samples was repeatedly detected in the south, in the county of Halland, which is one of the counties with the highest cattle density in the country. In order to understand the epidemiology of IDV, further research in different cattle populations and in humans is required. Full article

Bovine respiratory disease (BRD) is one of the most prevalent, deadly, and costly diseases in young cattle. BRD has been recognized as a multifactorial disease caused mainly by viruses (bovine herpesvirus, BVDV, parainfluenza-3 virus, respiratory syncytial virus, and bovine coronavirus) and bacteria (Mycoplasma bovis, Pasteurella multocida, Mannheimia haemolytica and Histophilus somni). However, other microorganisms have been recognized to cause BRD. Influenza D virus (IDV) is a novel RNA pathogen belonging to the family Orthomyxoviridae, first discovered in 2011. It is distributed worldwide in cattle, the main reservoir. IDV has been demonstrated to play a role in BRD, with proven ability to cause respiratory disease, a high transmission rate, and potentiate the effects of other pathogens. The transmission mechanisms of this virus are by direct contact and by aerosol route over short distances. IDV causes lesions in the upper respiratory tract of calves and can also replicate in the lower respiratory tract and cause pneumonia. There is currently no commercial vaccine or specific treatment for IDV. It should be noted that IDV has zoonotic potential and could be a major public health concern if there is a drastic change in its pathogenicity to humans. This review summarizes current knowledge regarding IDV structure, pathogenesis, clinical significance, and epidemiology. Full article

Both influenza C (ICV) and influenza D (IDV) viruses were recently included as bovine respiratory disease (BRD) causes, but their role in BRD has not been evaluated. Therefore, the mortality and reproductive performances of BRD calves with different isolated viruses were determined in this study. Data on 152 BRD calves with bovine viral diarrhoea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronavirus (BCoV), bovine parainfluenza virus 3 (BPIV-3), ICV, or IDV from nasal swab samples using real-time rt-PCR were used. The general data and respiratory signs were recorded immediately, and thereafter, the data on dead or culling calves due to BRD and reproductive performance were collected. The percentages of the BRD calves were 71.7%, 52.6%, 40.8%, 10.5%, 68.4%, and 65.8% for BVDV, BRSV, BCoV, BPIV-3, ICV, and IDV, respectively. Mucous secretion (OR = 4.27) and age ≤ 6 months (OR =14.97) had higher risks of mortality than those with serous secretion and older age. The calves with IDV had lower risks of culling than those without IDV (OR = 0.19). This study shows that most viral infections in BRD calves are a combination of viruses with BVDV, ICV, and IDV. In addition, IDV might have a role in reducing the severity of BRD calves. Full article

The newest type of influenza virus, influenza D virus (IDV), was isolated in 2011. IDV circulates in several animal species worldwide, causing mild respiratory illness in its natural hosts. Importantly, IDV does not cause clinical disease in humans and does not spread easily from person to person. Here, we review what is known about the host–pathogen interactions that may limit IDV illness. We focus on early immune interactions between the virus and infected host cells in our summary of what is known about IDV pathogenesis. This work establishes a foundation for future research into IDV infection and immunity in mammalian hosts. Full article