A Novel A(H7N2) Influenza Virus Isolated from a Veterinarian Caring for Cats in a New York City Animal Shelter Causes Mild Disease and Transmits Poorly in the Ferret Model

Abstract

In December 2016, a low-pathogenic avian influenza (LPAI) A(H7N2) virus was identified to be the causative source of an outbreak in a cat shelter in New York City, which subsequently spread to multiple shelters in the states of New York and Pennsylvania. One person with occupational exposure to infected cats became infected with the virus, representing the first LPAI H7N2 virus infection in a human in North America since 2003. Considering the close contact that frequently occurs between companion animals and humans, it was critical to assess the relative risk of this novel virus to public health. The virus isolated from the human case, A/New York/108/2016 (NY/108), caused mild and transient illness in ferrets and mice but did not transmit to naive cohoused ferrets following traditional or aerosol-based inoculation methods. The environmental persistence of NY/108 virus was generally comparable to that of other LPAI H7N2 viruses. However, NY/108 virus replicated in human bronchial epithelial cells with an increased efficiency compared with that of previously isolated H7N2 viruses. Furthermore, the novel H7N2 virus was found to utilize a relatively lower pH for hemagglutinin activation, similar to human influenza viruses. Our data suggest that the LPAI H7N2 virus requires further adaptation before representing a substantial threat to public health. However, the reemergence of an LPAI H7N2 virus in the northeastern United States underscores the need for continuous surveillance of emerging zoonotic influenza viruses inclusive of mammalian species, such as domestic felines, that are not commonly considered intermediate hosts for avian influenza viruses. IMPORTANCE Avian influenza viruses are capable of crossing the species barrier to infect mammals, an event of public health concern due to the potential acquisition of a pandemic phenotype. In December 2016, an H7N2 virus caused an outbreak in cats in multiple animal shelters in New York State. This was the first detection of this virus in the northeastern United States in over a decade and the first documented infection of a felid with an H7N2 virus. A veterinarian became infected following occupational exposure to H7N2 virus-infected cats, necessitating the evaluation of this virus for its capacity to cause disease in mammals. While the H7N2 virus was associated with mild illness in mice and ferrets and did not spread well between ferrets, it nonetheless possessed several markers of virulence for mammals. These data highlight the promiscuity of influenza viruses and the need for diligent surveillance across multiple species to quickly identify an emerging strain with pandemic potential.

Emergence and adaptation of H3N2 canine influenza virus from avian influenza virus: An overlooked role of dogs in interspecies transmission

“…Companion animals, such as cats and dogs, have been suggested to be a source of new avian‐origin AIVs, with the potential to cause severe respiratory disease in humans. In 2016, a veterinarian was infected with a low pathogenic avian influenza virus H7N2, which was also isolated from a cat shelter in New York City (Belser et al., ). Canines carrying avian‐origin H3N2 CIV have also the potential to transmit the virus to other species in frequent close contact such as cats (Jeoung et al., ; Park et al., ).…”

Detection of an avian lineage influenza A(H7N2) virus in air and surface samples at a New York City feline quarantine facility

“…Hatta et al assessed transmission of the A/feline/NY/2016 in ferrets and cats. In contrast to Belser et al 1 of 3 pairs of ferrets placed in direct contact showed productive infection and seroconversion but no respiratory droplet transmission to ferrets placed in adjacent cages. They suggested that amino acid differences in the PA, HA, and NA proteins between the human and cat isolates or the small group size may account for this difference.…”

“…By measuring particle size, distribution, and infectivity, our study suggests that A(H7N2) transmission had the potential to occur through aerosol transmission of small viral‐laden respiratory droplets and/or contact with viral‐laden fomites. Belser et al investigated the relative risk of transmission among workers using a ferret model of transmission and showed that ferrets intranasally inoculated with the A/NY/108/2016 virus became productively infected but did not transmit the virus to ferrets placed in an adjacent cage. However, naïve ferrets placed in the same cage with infected ferrets showed low‐titer virus in the nasal washes but did not seroconvert.…”

“…Belser et al also showed that direct aerosol inhalation of a high dose but not a low dose of virus led to productive infection but, as with nasal inoculation, transmission to cohoused contact ferrets did not result in their seroconversion. In an earlier study, Belser et al additionally showed that infection via the ocular route was possible in ferrets although they did not assess transmission.…”

“…Genome analysis of the initial feline isolate (A/feline/New York/16‐040082‐1/2016) and subsequent virological characterization of the human isolate (A/New York/108/2016) showed it to be phylogenetically related to the North American lineage low‐pathogenic avian influenza (LPAI) A(H7N2) viruses circulating in live poultry markets during 1996‐2005. Recent analysis of the human A(H7N2) isolate showed it to transmit poorly in ferrets but, unlike previously identified isolates, displayed an increased ability to replicate in human airway cells . While it is unknown how the index cat was exposed to the A(H7N2) virus, the high rate of transmission among cats and concern about a possible zoonotic transmission mandated quarantine precautions.…”