Thursday, December 14, 2017

EID Journal: Characterization Of A Feline Influenza A(H7N2) Virus


Almost exactly a year ago (Dec 15th, 2016) the New York City Health Department issued an unusual Statement On Avian H7N2 In Cats at a Manhattan animal shelter.
While cats are known to be susceptible to some novel  flu strains (see Catch As Cats Can) this outbreak was remarkable due to its size (initially involving 45 cats), its location (NYC), and the virus involved - a relatively uncommon avian LPAI H7N2 virus not reported in the United States in years. 
Over the Christmas holidays the story continued to escalate  when the NYC DOH released a statement announcing a mild Human H7N2 Infection in a veterinarian who was treating sick cats.  Additionally, more than 400 cats - across multiple facilities - were said to have been infected. 
Although the risk to human health was believed low, the Health Department offered guidance to those who have had contact with cats in these shelters, and urged people to avoid `nuzzling and close facial contact' with sick cats.
Human infection with LPAI H7N2 has only rarely been reported, with only a couple of cases  on record in the United States (in 2002 and 2003), and 4 people who were presumed to have been infected in the UK in 2007 following local outbreaks in poultry. In all cases, illness was described as mild and self limiting.

Last May, in J. Virology: Virulence Of A Novel H7N2 Virus Isolated From Cats In NYC - Dec 2016,  we saw a follow up report on the NYC outbreak, which found the H7N2 virus will require additional adaptation before it poses a substantial human health threat.   

A month ago, in EID Journal: Avian H7N2 Virus in Human Exposed to Sick Cats, we saw another study that found the human H7N2 virus bound to both α2,6-linked (mammalian) and α2,3-linked (avian) sialic acids, an important trait for any species jumping avian flu virus to acquire, although virulence remained low. 

Today we've a new analysis published in the EID Journal of the H7N2 virus isolated from cats.  As this is a lengthy and technical report, I've only posted a few excerpts.  Follow the link below to read it in its entirety.

Characterization of a Feline Influenza A(H7N2) Virus

Masato Hatta1, Gongxun Zhong1, Yuwei Gao1, Noriko Nakajima1, Shufang Fan1, Shiho Chiba, Kathleen M. Deering, Mutsumi Ito, Masaki Imai, Maki Kiso, Sumiho Nakatsu, Tiago J. Lopes, Andrew J. Thompson, Ryan McBride, David L. Suarez, Catherine A. Macken, Shigeo Sugita, Gabriele Neumann, Hideki Hasegawa, James C. Paulson, Kathy L. Toohey-Kurth, and Yoshihiro Kawaoka


During December 2016–February 2017, influenza A viruses of the H7N2 subtype infected ≈500 cats in animal shelters in New York, NY, USA, indicating virus transmission among cats. A veterinarian who treated the animals also became infected with feline influenza A(H7N2) virus and experienced respiratory symptoms. 

To understand the pathogenicity and transmissibility of these feline H7N2 viruses in mammals, we characterized them in vitro and in vivo. Feline H7N2 subtype viruses replicated in the respiratory organs of mice, ferrets, and cats without causing severe lesions. 

Direct contact transmission of feline H7N2 subtype viruses was detected in ferrets and cats; in cats, exposed animals were also infected via respiratory droplet transmission. These results suggest that the feline H7N2 subtype viruses could spread among cats and also infect humans. Outbreaks of the feline H7N2 viruses could, therefore, pose a risk to public health.


We assessed feline H7N2 subtype viruses isolated from infected cats during the outbreak for their replicative ability, pathogenicity, and transmissibility in mammals; in contrast to the findings recently published by Belser et al. (7), we detected productive infection of co-housed ferrets, although with low efficiency.
We also conducted extensive pathology and transmission studies in cats, and detected feline virus transmission via respiratory droplets to exposed cats. Our study provides additional data on the risk that the feline H7N2 subtype viruses pose to public health.



In our study, we demonstrated that a feline H7N2 subtype virus isolated during an outbreak in an animal shelter in New York in December 2016 replicated well in the respiratory organs of mice and ferrets but did not cause severe symptoms.
The efficient replication of the feline H7N2 subtype viruses in the respiratory organs of several mammals, combined with the ability of these viruses to transmit among cats (albeit inefficiently) and to infect 1 person, suggest that these viruses could pose a risk to human health. Close contacts between humans and their pets could lead to the transmission of the feline viruses to humans. To protect public health, shelter animals (where stress and limited space may facilitate virus spread) should be monitored closely for potential outbreaks of influenza viruses.
Our findings of mild disease in mice and ferrets are consistent with the recent report by Belser et al. (7) who studied the H7N2 subtype virus isolated from an infected veterinarian. We also assessed feline H7N2 virulence in cats and detected efficient virus replication in both the upper and lower respiratory organs of infected animals, whereas an avian H7N2 subtype virus was detected mainly in the nasal turbinates.
Belser et al. (7) reported that intranasal or aerosol infection of ferrets with the H7N2 virus isolated from the infected veterinarian did not result in the seroconversion of co-housed or exposed animals, although nasal wash samples from some of the co-housed ferrets contained low titers of virus; these findings may suggest limited virus transmission that was insufficient to establish a productive infection.
In contrast, we detected feline H7N2 virus transmission to co-housed ferrets in 1 of 3 pairs tested; this difference may be explained by the amino acid differences in the PA, HA, and NA proteins of the feline and human H7N2 isolates (Technical Appendix[PDF - 3.63 MB - 35 pages] Table 4) or by the small number of animals used in these studies. We also performed transmission studies in cats and detected feline H7N2 subtype virus transmission via direct contact and respiratory droplets. However, the group size used is a potential limitation of our study.
Cats are not a major reservoir of influenza A viruses, but can be infected naturally or experimentally with influenza viruses of different subtypes (23). Serologic surveys suggest high and low rates of seroconversion to seasonal human and highly pathogenic avian influenza viruses, respectively. Natural infections most likely result from close contact with infected humans or animals, and most of these infections appear to be self-limiting.
Few cases of human infections with influenza viruses of the H7 subtype were reported until 2013, and they typically caused mild illness; however, infection of a veterinarian with a highly pathogenic avian H7N7 virus had fatal consequences (24,25).
Since 2013, influenza viruses of the H7N9 subtype have caused more than 1,300 laboratory-confirmed infections in humans, with a case-fatality rate of ≈30%. Although the current H7N9 and feline H7N2 subtype viruses do not exclusively bind to human-type receptors and do not transmit efficiently among humans, the spread and biologic properties of these viruses should be monitored carefully.
Dr. Hatta is a senior scientist at the Influenza Research Institute at the University of Wisconsin, Madison, WI. His research focuses on identifying the molecular determinants of influenza virus pathogenicity, with particular emphasis on the pathogenicity of highly pathogenic influenza viruses.
As pointed out in earlier blogs on this event, avian H7N2 doesn't appear to be ready for prime time, but it has evolved considerably since its previous appearances in U.S. poultry nearly 15 years ago.
In last May's J. Virology study the virus reportedly replicated with increased efficiency in human bronchial epithelial cells over previous H7N2 strains tested, and were better adapted to using a lower pH for HA activation, similar to seasonal flu viruses.
While we tend to focus our attention on a small number of high profile novel viruses (H7N9, H5Nx, H9N2, etc.), influenza evolution an open field event.

Any number of viruses can play.

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