Pathogenesis of Influenza D Virus in Cattle

Abstract

Cattle have been proposed as the natural reservoir of a novel member of the virus family Orthomyxoviridae, which has been tentatively classified as influenza D virus (IDV). Although isolated from sick animals, it is unclear whether IDV causes any clinical disease in cattle. To address this aspect of Koch's postulates, three dairy calves (treatment animals) held in individual pens were inoculated intranasally with IDV strain D/bovine/Mississippi/C00046N/2014. At 1 day postinoculation, a seronegative calf (contact animal) was added to each of the treatment animal pens. The cattle in both treatment and contact groups seroconverted, and virus was detected in their respiratory tracts. Histologically, there was a significant increase in neutrophil tracking in tracheal epithelia of the treatment calves compared to control animals. While infected and contact animals demonstrated various symptoms of respiratory tract infection, they were mild, and the calves in the treatment group did not differ from the controls in terms of heart rate, respiratory rate, or rectal temperature. To mimic zoonotic transmission, two ferrets were exposed to a plastic toy fomite soaked with infected nasal discharge from the treatment calves. These ferrets did not shed the virus or seroconvert. In summary, this study demonstrates that IDV causes a mild respiratory disease upon experimental infection of cattle and can be transmitted effectively among cattle by in-pen contact, but not from cattle to ferrets through fomite exposure. These findings support the hypothesis that cattle are a natural reservoir for the virus. IMPORTANCE A novel influenza virus, tentatively classified as influenza D virus (IDV), was identified in swine, cattle, sheep, and goats. Among these hosts, cattle have been proposed as the natural reservoir. In this study, we show that cattle experimentally infected with IDV can shed virus and transmit it to other cattle through direct contact, but not to ferrets through fomite routes. IDV caused minor clinical signs in the infected cattle, fulfilling another of Koch's postulates for this novel agent, although other objective clinical endpoints were not different from those of control animals. Although the disease observed was mild, IDV induced neutrophil tracking and epithelial attenuation in cattle trachea, which could facilitate coinfection with other pathogens, and in doing so, predispose animals to bovine respiratory disease.

The pulmonary virome, bacteriological and histopathological findings in bovine respiratory disease from western Canada

“…At that point, viruses, if any, might have already been cleared, leaving only the pulmonary lesions. Secondly, some viruses, such as IDV (Ferguson et al, ), preferentially infect the upper respiratory tract, not the lung. In the current study, IDV was detected in the lung of only 1/130 cattle, compared with 16/116 upper respiratory tract samples in our previous study (Zhang et al, ).…”

Molecular epidemiological survey and phylogenetic analysis of bovine influenza D virus in Japan

“…Previous studies have reported that 0.6% and 2.4% of healthy cattle were infected by this virus (Ferguson et al., ; Jiang et al., ). An experimental infection with this virus showed that several infected cattle were asymptomatic (Ferguson et al., ). In this study, follow‐up evaluations of the health statuses of the cattle after sampling were not conducted.…”

Serological evidence for high prevalence of Influenza D Viruses in Cattle, Nebraska, United States, 2003–2004

“…Laboratory studies demonstrated cattle, swine, ferrets, and guinea pigs are susceptible to IDV infection (Collin et al, 2015; Ferguson et al, 2016; Hause et al, 2014; Hause et al, 2013; Sreenivasan et al, 2015). Serologic assays in two independent studies showed that IDV could potentially infect humans, although seropositivity rates in the studies differed.…”

“…One of the studies reported 91% seropositivity among 35 persons working with cattle (White et al, 2016), and the other reported only 1% seropositivity among 741 persons with suspected high exposure to IDV (Eckard, 2016). Nevertheless, epidemiologic, serologic, and pathologic studies have suggested cattle are the primary natural reservoir for IDV (Collin et al, 2015; Ducatez et al, 2015; Ferguson et al, 2015; Ferguson et al, 2016; Hause et al, 2014; Jiang et al, 2014). …”

“…Laboratory studies suggested that IDV can be efficiently transmitted in cattle, with viral replications in the upper and lower respiratory tracts (Ferguson et al, 2016). An earlier study suggested that IDV was detected at higher frequency in cattle with bovine respiratory disease (BRD) than healthy cattle (Ferguson et al, 2015), which was consistent with the findings in two metagenomic studies (Mitra et al, 2016; Ng et al, 2015).…”