Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model

Sreenivasan, Chithra; Thomas, M. G.; Sheng, Zizhang; Hause, Ben M.; Collin, Emily A.; Knudsen, David; Pillatzki, Angela; Nelson, Eric; Wang, Dan Dan; Kaushik, Radhey S.; Li, Feng

doi:10.1128/jvi.01630-15

Cited by 69 publications

(83 citation statements)

References 28 publications

(60 reference statements)

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“…The age of cattle used in the experiments could account for such a discrepancy, and it is also notable that our calves were naturally born and given thawed colostrum at birth. On the other hand, our data are similar to swine and ferret IDV experimental infection models but unlike an IDV guinea pig model in which the highest viral titer was found in lung tissue despite intranasal inoculation (11). Structural modeling suggested that, similar to ICV, IDV binds to 9-O-acetyl sialic acid (1).…”

Section: Discussionsupporting

confidence: 66%

“…IDV was detected in nasal turbinate, trachea, bronchus, and right medial lung lobe tissues collected at 4 dpi, and IHC confirmed the presence of IDV antigen in all the tissues except RMD. In other animal models, IDV was shown to replicate within the nasal turbinate; could be detected in nasal washes from infected swine, ferret, and guinea pig; and could also be transmitted through direct contact among members of the same species (1,11). We were able to detect IDV in the right medial lung lobe at 4 dpi via both quantitative RT-PCR and TCID 50 , but no antigen was seen via IHC and there was no evidence of pulmonary pathology, again suggestive of an upper respiratory tract infection.…”

Section: Discussionmentioning

confidence: 99%

“…It is also possible that the virus gained host adaptations upon transmission that could have facilitated more efficient replication. Phenotypic changes in influenza viruses due to adaptation to the host have been shown in IAV studies in feral swine, domestic swine, and mice and have also been demonstrated for IDV in the guinea pig transmission model (11)(12)(13)(14). Future studies will characterize the pathogenesis in the contact calves and potentially identify mutations in the isolates recovered from the contact calves.…”

Section: Discussionmentioning

confidence: 99%

“…Ferrets have a respiratory system similar to that of humans and are widely used in influenza studies (15). Because IDV was first identified only in 2011, little is known about the virus despite its cellular and host tropisms (1,2,8,11). Studies have highlighted the need for understanding the host tropism and the zoonotic potential of IDV.…”

Section: Discussionmentioning

confidence: 99%

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Pathogenesis of Influenza D Virus in Cattle

Ferguson

Olivier

Genova

et al. 2016

J Virol

141

187

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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.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pathogenesis of Influenza D Virus in Cattle

Ferguson

Olivier

Genova

et al. 2016

J Virol

141

187

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“…(24) zakazili donosowo świnki morskie IDV. W tej samej klatce umieścili zwierzęta kontrolne, celem oceny możliwości zakażenia drogą kontaktu bezpośredniego.…”

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Prevalence of infections with a new type of influenza virus – influenza D virus in humans and animals

Markowska-Daniel¹,

Mickiewicz²,

Witkowski³

et al. 2016

Medycyna Weterynaryjna

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In April 2011, in the USA, a new influenza virus type D (IDV) was isolated for the first time from pigs and then from cows. In the paper the data about the prevalence of this virus in humans and animals are described. It was evidenced that HE protein of IDV could bind to cellular receptors in the epithelium of the human trachea. Moreover, the new virus was shown to infect and spread in ferrets. These findings make it possible to conclude that IDV seems to be able to infect humans and have zoonotic potential. Up to now the percent of human seroconverted to IDV has been low, about 1.3%. The susceptibility of pigs to IDV has been shown in natural and experimental conditions. Virus specific antibodies were detected in 9.5% of pigs. Additionally the isolates from pigs were obtained in the USA and Italy. This suggests that pigs are not the natural reservoir of this virus and the infections are uncommon in pig populations. Several studies demonstrated that the new virus is widely spread in cattle. It was isolated in the USA, Canada, China, France and Italy, which proved that the intercontinental transmission of IDV had occurred. The highest percentage of infected cows, mainly animals manifesting BRDC symptoms, was found in Minnesota, Oklahoma and Mississippi, and it varied from 4.8 to 29.1%. Additionally the virus was detected in 2.4% of healthy animals. Seroconversion was demonstrated in 32.7 to 87.5% of the bovine herds tested in Mississippi and Minnesota, respectively. Retrospective analysis revealed that antibodies specific to IDV had been detected in bovine samples since 2004. This suggests that the new virus has circulated in cattle at least since 2004. The analysis of the relationship between the seroconversion and the age of animals showed that over 50% of cows aged 1–14 years were seropositive. Also more than 90% of newborn calves had maternal antibodies to IDV. The spread of IDV was also linked to the type of farm, with the lowest percentage of animals seroconverting in closed herds and the highest in order-buying facilities. Therefore cattle seem to be the natural host of IDV. In the USA and Canada the infections caused by IDV were also found in sheep and goats. Herd-level and individual-level seroprevalence in sheep was 15.3 and 6.1%, respectively, and these figures were even higher in goats: 20% and 25.9%, respectively. This shows that small ruminants are susceptible to IDV infection. Moreover, retrospective analysis confirmed that one serum from a goat taken in Massachusetts in 2002 was positive to IDV. This suggests that the new virus may have circulated among goats as early as in 2002. Serological studies of chicken and turkey sera from the herds in Minnesota, located near the positive bovine herds, yielded negative results. This might suggest that birds are resistant to IDV infection; however, the number of birds tested is insufficient to substantiate such a statement. The studies aimed at evaluation of zoonotic potential of the new virus proved that it replicated efficiently in the upper respiratory tract of ferrets. This suggests that the new virus may have an influence on public health. In experimental conditions the susceptibility of guinea pigs to IDV infection was also evidenced. In conclusion, all the studies demonstrated that cattle were the natural reservoir of the new virus, despite the fact that humans as well as various animal species could also be infected. Furthermore, cattle are likely to be a potential source of infection for both animals and humans.

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Porcine mast cells infected with H1N1 influenza virus release histamine and inflammatory cytokines and chemokines

2017

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Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines. Inflammatory cytokine- and chemokine-encoding genes, including IL-1α, IL-6, CXCL9, CXCL10, and CXCL11, were upregulated in the infected porcine mast cells. Our results suggest that mast cells could be involved in enhancing influenza-virus-mediated disease in infected animals.

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Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model

Cited by 69 publications

References 28 publications

Pathogenesis of Influenza D Virus in Cattle

Pathogenesis of Influenza D Virus in Cattle

Prevalence of infections with a new type of influenza virus – influenza D virus in humans and animals

Porcine mast cells infected with H1N1 influenza virus release histamine and inflammatory cytokines and chemokines

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