Insights into the Acquisition of Virulence of Avian Influenza Viruses during a Single Passage in Ferrets.

Circulating avian influenza viruses pose a significant threat, with human infections occurring infrequently but with potentially severe consequences. To examine the dynamics and locale of the adaptation process of avian influenza viruses when introduced to a mammalian host, we infected ferrets with H5N1 viruses. As expected, all ferrets infected with the human H5N1 isolate A/Vietnam/1203/2004 showed severe disease and virus replication outside the respiratory tract in multiple organs including the brain.

Efficacy of a specific polyclonal equine F(ab')2 against avian influenza (H5N1) in ferrets: synergy with oseltamivir.

Aim: Current therapies against avian influenza (H5N1) provide limited clinical benefit. FBF-001 is a highly purified equine polyclonal immunoglobulin fragment against H5N1.

Methods: Using a ferret model of severe acute H5N1 infection, we assessed FBF-001 when administered on the same day or 1 day after viral challenge, in comparison with oseltamivir therapy.

Experimental Infection and Response to Rechallenge of Alpacas with Middle East Respiratory Syndrome Coronavirus.

We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. The alpacas shed virus at challenge but were refractory to further shedding at rechallenge on day 21. The trial indicates that alpacas may be suitable models for infection and shedding dynamics of this virus.

Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes.

Unlabelled: Although avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome.

Isolation of multiple novel paramyxoviruses from pteropid bat urine.

Bats have been found to harbour a number of new emerging viruses with zoonotic potential, and there has been a great deal of interest in identifying novel bat pathogens to determine the risk to human and animal health. Many groups have identified novel viruses in bats by detection of viral nucleic acid; however, virus isolation is still a challenge, and there are few reports of viral isolates from bats. In recent years, our group has developed optimized procedures for virus isolation from bat urine, including the use of primary bat cells.

Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact.

Objectives: The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting.

Hendra virus vaccine, a one health approach to protecting horse, human, and environmental health.

In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population.

Vaccination of ferrets with a recombinant G glycoprotein subunit vaccine provides protection against Nipah virus disease for over 12 months.

Background: Nipah virus (NiV) is a zoonotic virus belonging to the henipavirus genus in the family Paramyxoviridae. Since NiV was first identified in 1999, outbreaks have continued to occur in humans in Bangladesh and India on an almost annual basis with case fatality rates reported between 40% and 100%.

Methods: Ferrets were vaccinated with 4, 20 or 100 μg HeVsG formulated with the human use approved adjuvant, CpG, in a prime-boost regime.

Promotion of Hendra virus replication by microRNA 146a.

Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication.

Transmission routes for nipah virus from Malaysia and Bangladesh.

Human infections with Nipah virus in Malaysia and Bangladesh are associated with markedly different patterns of transmission and pathogenicity. To compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the Malaysia or Bangladesh strain of Nipah virus. Viral shedding and tissue tropism were compared between the 2 groups.

Multiple routes of invasion of wild-type Clade 1 highly pathogenic avian influenza H5N1 virus into the central nervous system (CNS) after intranasal exposure in ferrets.

Human infections with highly pathogenic avian influenza (HPAI) H5N1 have been associated with central nervous system involvement. The purpose of this study was to examine the route of invasion of wild-type HPAI H5N1 virus into the central nervous system (CNS) using a ferret model of infection. Sixteen ferrets were exposed by the intranasal route to 10(6) TCID(50) of A/Vietnam/1203/04, a Clade 1 strain originally isolated from a fatal human case.

Experimental infection of horses with Hendra virus/Australia/horse/2008/Redlands.

Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus harbored by Australian flying foxes with sporadic spillovers directly to horses. Although the mode and critical control points of HeV spillover to horses from flying foxes, and the risk for transmission from infected horses to other horses and humans, are poorly understood, we successfully established systemic HeV disease in 3 horses exposed to Hendra virus/Australia/Horse/2008/Redlands by the oronasal route, a plausible route for natural infection. In 2 of the 3 animals, HeV RNA was detected continually in nasal swabs from as early as 2 days postexposure, indicating that systemic spread of the virus may be preceded by local viral replication in the nasal cavity or nasopharynx.

Ebola Reston virus infection of pigs: clinical significance and transmission potential.

In 2008, Reston ebolavirus (REBOV) was isolated from pigs during a disease investigation in the Philippines. Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV-2) infections were also confirmed in affected herds and the contribution of REBOV to the disease outbreak remains uncertain. We have conducted experimental challenge studies in 5-week-old pigs, with exposure of animals to 10(6) TCID(50) of a 2008 swine isolate of REBOV via either the oronasal or subcutaneous route.

A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both.