Protection of ferrets against influenza challenge with a DNA vaccine to the haemagglutinin

Immunization of ferrets with a plasmid DNA expressing influenza virus haemagglutinin (pCMV/H1 DNA) provided complete protection from challenge with the homologous A/PR/8/34 (HINI) influenza virus. Delivery of DNA-coated gold beads by gene gun to the epidermis was much more efficient than intramuscular delivery of DNA in aqueous solution. The antibody response induced by DNA delivered by gene gun was more cross-reactive than DNA delivered in aqueous solution or after natural infection. This novel approach to vaccination against influenza may afford broader protection against antigenic drift than that provided by natural infection.     

Minimal molecular constraints for respiratory droplet transmission of an avian–human H9N2 influenza A virus

Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian–human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.     

Novel hepatitis e virus in ferrets, the Netherlands

TO THE EDITOR: Hepatitis E virus (HEV), a member of the family Hepeviridae and the genus Hepevirus, is transmitted by the fecal-oral route and causes liver inflammation, which leads to mortality rates of ≤20% in pregnant woman (1,2). Human hepatitis E is a major disease not only in developing countries but also in industrialized countries, and identification of animal strains of HEV in pigs and deer and its zoonotic potential has raised considerable public health concerns (1,3). Recent reports suggest that other animals such as rats, mongooses, chickens, rabbits, and trout also may harbor HEVs (1-5). The genomes of these viruses are ≈6.6 kb-7.2 kb and encode 3 open reading frames (ORFs) flanked by a capped 5' end and a poly A tail at the 3' end (1,3). We used random PCR amplification and high-throughput sequencing technology to investigate HEV sequences in ferrets (Mustela putorius) from the Netherlands.     

Complete Genome of Hepatitis E Virus from Laboratory Ferrets

The complete genome of hepatitis E virus (HEV) from laboratory ferrets imported from the United States was identified. This virus shared only 82.4%–82.5% nt sequence identities with strains from the Netherlands, which indicated that the ferret HEV genome is genetically diverse. Some laboratory ferrets were contaminated with HEV.     

Natural SARS-CoV-2 Infection in Kept Ferrets,Spain

We found severe acute respiratory syndrome coronavirus 2 RNA in 6 (8.4%) of 71 ferrets in central Spain and isolated and sequenced virus from 1 oral and 1 rectal swab specimen. Natural infection occurs in kept ferrets when virus circulation among humans is high. However, small ferret collections probably cannot maintain virus circulation.     

Development of the lateral geniculate nucleus: interactions between retinal afferent, cytoarchitectonic, and glial cell process lamination in ferrets and tree shrews.

We have studied the relationship of retinal afferents, glial cell processes, and neuronal cytoarchitectonics in the lateral geniculate nucleus (LGN) of two species: tree shrews (Tupaia belangeri) and ferrets (Mustela putoris). Both species are relatively immature at birth, allowing the development of these features to be studied in the perinatal period. Retinal afferents, visualized by intraocular injection of a wheat germ agglutinin/horseradish peroxidase conjugate (WGA-HRP), are apparently the first elements of the developing LGN to exhibit a characteristic layered pattern in tree shrews and ferrets. Some radial glia still remain in the LGN of both species as the retinal afferents are in the process of segregating. Glial cell processes were visualized immunohistochemically with antibodies to glial fibrillary acidic protein (GFAP) or vimentin. In both the ferret and tree shrew, layering of glial cell processes is first seen as the overlap of retinal terminal fields diminishes. In the tree shrew LGN, these bands of dense glial cell staining are seen in apparent future cellular layers, whereas in the ferret, glial cell banding appears in interlaminar zones. If one or both eyes are removed at birth in tree shrews (before LGN cell layers are formed), the glial cell pattern seen 1 week later is in accord with the distribution of surviving nerve cells. The glial processes do not appear to invade regions left by degenerating retinal terminals or dying LGN cells. Several days after the appearance of layered glial cell processes (in the tree shrew) or at about the same time as glial layering (in the ferret), the first interlaminar spaces develop between neuronal cells, marking the beginning of cytoarchitectonic lamination, with its distinctive alternating cell-rich and cell-poor zones. Over the next several weeks, LGN neurons in both species continue to segregate into characteristic layers until the final, adult pattern of neuronal lamination is evident; as this process is completed, glial cell lamination disappears. These observations suggest that glial cells may be involved in establishing the neuronal layers that characterize the mature LGN of many species.     

L-dopa and apomorphine disrupt long—but not short—behavioural chains

Apomorphine (0.01–0.5 mg/kg) disrupted fighting between two male ferrets. The number of bites and neck nuzzling were decreased dose-dependently. At 0.05 and 0.1 mg/kg scent-marking and collateral behaviour were increased, at 0.5 mg/kg stereotyped sniffing was induced. L-dopa (120 mg/kg+30 mg/kg benserazide) exerted similar effects to apomorphine 0.05 mg/kg. Thus, the dopamine (DA) agonists increased short chain responses but disrupted long ones. Haloperidol (0.2 mg/kg) facilitated inter-male fighting. The number of bites increased, but scent-marking and collateral behaviour were selectively suppressed. Thus, the persistency of the long behavioural chain was enhanced. Since, at lower doses, DA-agonists expand and DA-antagonists selectively narrow the range of exhibited behavioural responses, it is suggested that the degree of stimulation of central DA-receptors determines the animal's ability to suppress responses that compete with ongoing behaviour.     

Small animal models of filovirus disease: recent advances and future directions

ABSTRACT

Introduction: Small animal models have played a critical role in understanding the pathogenesis and transmission of disease caused by filoviruses. Notably, small animals have served to identify and validate many different approaches to countering infection with these highly pathogenic viruses. Nonetheless, predictive efficacy between each model does not appear to be equivalent as higher order animals seem to be more prognostic and therefore successful in the evaluation of medical countermeasures (MCM).

Areas covered: This review comprehensively details the available small animal models of filovirus infection and discusses the benefits and shortcomings of each model with respect to the development of MCM. An up-to-date evaluation of mouse, hamster, guinea pig, and ferret models is provided.

Expert opinion: The recent development of the domestic ferret model for ebolavirus offers a small animal model that faithfully reproduces most features of human disease without the need for viral adaptation or an immunocompromised host. That being said, choosing a small animal model to evaluate a particular MCM must consider potential confounders associated with each model. These confounding issues include incomplete host immune systems or mutations in the challenge virus that enables the disease.     

Inter‐ and intraspecies transmission of canine influenza virus (H3N2) in dogs,cats, and ferrets

Background The emergence of zoonotic viruses in domestic animals is a significant public health concern. Canine influenza virus (CIV) H3N2 is a virus that can infect companion animals and is, therefore, a potential public health concern. Objective This study investigated the inter‐ and intraspecies transmission of CIV among dogs, cats, and ferrets, under laboratory conditions, to determine whether transmission of the virus was possible between as well as within these domestic animal species. Method The transmission routes for inter‐ and intraspecies transmission were airborne and direct contact, respectively. Transmission was conducted through intranasal infection of dogs followed by exposure to either cats or ferrets and by comingling infected and naïve animals of the same species. Results The interspecies transmission of CIV H3N2 via airborne was only observed from dogs to cats and not from dogs to ferrets. However, direct intranasal infection of either cats or ferrets with CIV could induce influenza‐like clinical signs, viral shedding, and serological responses. Additionally, naïve cats and ferrets could be infected by CIV via direct contact with infected animals of the same species. Conclusion Cats appear to be another susceptible host of CIV H3N2, whereas ferrets are not likely natural hosts. The molecular‐based mechanism of interspecies and intraspecies transmission of CIV H3N2 should be further studied.