Wednesday, November 23, 2016

J. Virol: Potential For LPAI H7 To Cause Disease In A Mammalian Model

LPAI H7N9 Epidemic Waves












#11,936



Until LPAI H7N9 appeared in China during the winter/spring of 2013, Low Path H7 viruses were generally regarded as a `weak sister' to the H5 avian viruses, and primarily a risk to poultry. 

Human infection with any H7 virus (LP or HP) until then had been rare, and generally mild. 

All of that changed when LPAI H7N9 - which is carried asymptomatically in birds - began infecting humans and driving a yearly epidemic (see WHO chart above) in China.

This raises the obvious question that if a low path H7N9 could cause substantial illness and death in humans, what other LPAI H7 viruses out there have some potential to pose a human health threat?

In an attempt to answer this question, researchers tested 30 LPAI H7 viruses collected from North America on DBA/2J mice, and found 90% of them produced varying degrees of mortality.
 
Remarkably 75% (24 of 30) were as pathogenic as the 2013 Anhui strain of H7N9.  Duck borne viruses tended to be more pathogenic than shorebird viruses. 

These viruses replicated beyond the respiratory system of these mice (including in their hearts and brains), and while they bound preferentially to avian α2,3 receptor cells, they demonstrated some ability to bind to mammalian α2,6 receptors.

All of which means that the threat from low path H7 viruses may have been underappreciated in the past, and that they pose a potential public health risk.

The full study is behind a paywall, but most of the details are available in the abstract.



J Virol. 2016 Nov 16. pii: JVI.01934-16. [Epub ahead of print]
The Potential for Low Pathogenic Avian H7 Influenza A Viruses to Replicate and Cause Disease in a Mammalian Model.

Abstract

H7 subtype influenza A viruses are widely distributed and have been responsible for human infections and numerous outbreaks in poultry with significant impact. Despite this, the disease-causing potential of the precursor low pathogenic (LP) H7 viruses from the wild bird reservoir has not been investigated. 

Our objective was to assess the disease causing potential of 30 LP H7 viruses isolated from wild avian species in the USA and Canada, using the DBA/2J mouse model. Without prior mammalian adaptation, the majority of viruses, 27 (90%), caused mortality in mice. 

Of these, 17 (56.7%) caused 100% mortality and 24 were of similar pathogenicity to A/Anhui/1/2013 (H7N9), which is highly pathogenic in mice. Viruses of duck-origin were more pathogenic than those of shorebird-origin, as 13 of 18 (72.2%) duck-origin viruses caused 100% mortality whilst 4 of 12 (33.3%) shorebird-origin viruses caused 100% mortality, despite there being no difference in mean lung viral titers between these groups. 

Replication beyond the respiratory tract was also evident, particularly in the heart and brain. Of the 16 viruses studied for fecal shedding, 11 were detected in fecal samples. These viruses exhibited a strong preference for avian-type α2,3-linked sialic acids, however, binding to mammalian-type α2,6-linked sialic acids was also detected. 

These findings indicate that LP avian H7 influenza A viruses are able to infect and cause disease in mammals without prior adaptation and therefore pose a potential public health risk.

IMPORTANCE: 

Low pathogenic (LP) avian H7 influenza A viruses are widely distributed in the avian reservoir and are the precursors of numerous outbreaks of highly pathogenic avian influenza viruses in commercial poultry farms. However, unlike highly pathogenic H7 viruses, the disease-causing potential of LP H7 viruses from the wild bird reservoir has not been investigated. 

To address this we studied 30 LP avian H7 viruses isolated from wild avian species in the USA and Canada using the DBA/2J mouse model. Surprisingly, the majority of these viruses, 90%, caused mortality in mice without prior mammalian adaptation and 56.7% caused 100% mortality. There was also evidence of spread beyond the respiratory tract and fecal shedding. 

Therefore, the disease-causing potential of LP avian H7 influenza A viruses in mammals may be underestimated and these viruses therefore pose a potential public health risk.

PMID:
27852855
DOI:
10.1128/JVI.01934-16
[PubMed - as supplied by publisher]

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