Pathogenesis, Host Innate Immune Response, and Aerosol Transmission of Influenza D Virus in Cattle

Abstract

The recently discovered influenza D virus (IDV) of the Orthomyxoviridae family has been detected in swine and ruminants with a worldwide distribution. Cattle are considered to be the primary host and reservoir, and previous studies suggested a tropism of IDV for the upper respiratory tract and a putative role in the bovine respiratory disease complex. This study aimed to characterize the pathogenicity of IDV in naive calves as well as the ability of this virus to transmit by air. Eight naive calves were infected by aerosol with a recent French isolate, D/bovine/France/5920/2014. Results show that IDV replicates not only in the upper respiratory tract but also in the lower respiratory tract (LRT), inducing moderate bronchopneumonia with restricted lesions of interstitial pneumonia. Inoculation was followed by IDV-specific IgG1 production as early as 10 days postchallenge and likely both Th1 and Th2 responses. Study of the innate immune response in the LRT of IDV-infected calves indicated the overexpression of pathogen recognition receptors and of chemokines CCL2, CCL3, and CCL4, but without overexpression of genes involved in the type I interferon pathway. Finally, virological examination of three aerosol-sentinel animals, housed 3 m apart from inoculated calves (and thus subject to infection by aerosol transmission), and IDV detection in air samples collected in different areas showed that IDV can be airborne transmitted and infect naive contact calves on short distances. This study suggests that IDV is a respiratory virus with moderate pathogenicity and probably a high level of transmission. It consequently can be considered predisposing to or a cofactor of respiratory disease. IMPORTANCE Influenza D virus (IDV), a new genus of the Orthomyxoviridae family, has a broad geographical distribution and can infect several animal species. Cattle are so far considered the primary host for IDV, but the pathogenicity and the prevalence of this virus are still unclear. We demonstrated that under experimental conditions (in a controlled environment and in the absence of coinfecting pathogens), IDV is able to cause mild to moderate disease and targets both the upper and lower respiratory tracts. The virus can transmit by direct as well as aerosol contacts. While this study evidenced overexpression of pathogen recognition receptors and chemokines in the lower respiratory tract, IDV-specific IgG1 production as early as 10 days postchallenge, and likely both Th1 and Th2 responses, further studies are warranted to better understand the immune responses triggered by IDV and its role as part of the bovine respiratory disease complex. FIG 1 (A) Experiment timeline and sampling. D0 is the day of inoculation. (B)Fourteen naive calves were allocated to two separated pens, one with 5 mock-infected calves (control group) and the second with 11 calves. In the latter pen, calves were divided into two groups separated by steel panels, 3 m apart. Eight calves (direct-inoculated group) were inoculated at day 0 (D0) with 10 7 TCID 50 of IDV 5...

Risk Mapping of Influenza D Virus Occurrence in Ruminants and Swine in Togo Using a Spatial Multicriteria Decision Analysis Approach

“…IDV is also transmissible by aerosol between cattle. [8,12,13,16,26,27] Small ruminants density Specific antibodies against IDV were detected in small ruminants, justifying their density as a risk factor. [3,26] Presence of respiratory clinical signs in cattle Several studies report that IDV is more commonly isolated from cattle with respiratory clinical signs and can be airborne transmitted among cattle.…”

“…All sera were treated with receptor destroying enzyme (RDE, Seika) following the manufacturer's instructions, diluted 10 folds, and hemadsorbed on packed chicken red blood cells. Hemagglutination inhibition (HI) assays were performed as previously described [16], with four hemagglutination units of D/bovine/France/5920/2014 and 1% chicken red blood cells. Based on our previous study carried out on African sera, a single antigen was used in HI tests, although two distinct genetic and antigenic lineages of IDV have been reported so far in North America and Europe (D/swine/OK and D/bovine/660) [7] (no significant differences were observed between the 2 antigens in HI assays on African sera [2]).…”

“…[3,26] Presence of respiratory clinical signs in cattle Several studies report that IDV is more commonly isolated from cattle with respiratory clinical signs and can be airborne transmitted among cattle. [8,[16][17][18] Cattle age Calves appear more susceptible to IDV infection than adults. [8,27] Proximity to cattle market In wildlife, IDV has been detected only in feral swine but because of the wide range of hosts susceptible to infection, wild ruminants and other species from wildlife could play a role in transmission.…”

“…Experimental infection with IDV is associated with mild to moderate pathogenicity in calves [8,16] and in the field, IDV is more often detected in cattle with respiratory clinical signs rather than without (OR = 2.94), although not significantly [17]. IDV has, thus, been postulated to play a role in the bovine respiratory complex [8,[16][17][18].…”

Detection of influenza D virus in bovine respiratory disease samples, UK

“…Although 21 different viruses were detected, including those normally associated with BRD, statistical analysis of the association between virus detection in animals not exhibiting clinical signs and acutely ill animals found that only IDV was a risk factor of significance. Recent experimental infections in cattle using aerosolized virus have confirmed that IDV can induce moderate clinical disease in the absence of other pathogens and has tropism for both the upper and lower respiratory tract (Salem et al., ).…”