Tuesday, March 17, 2015

Virology: Pathogenesis Of Avian A/H5N8 In Ferrets



# 9836


Despite being closely related to avian virus subtypes (H5N1, H5N6) that have produced serious morbidity and mortality in humans, the recently emerged H5N8 virus which has spread to both Europe and North America (see EID Journal: Novel Eurasian HPAI A H5 Viruses in Wild Birds – Washington, USA)  has never been linked to human infection or illness. 

Although not currently considered a serious threat to human health threat, the CDC has issued specific guidance documents for dealing with those who may have been exposed (see CDC Interim Guidance For Testing For Novel Flu & CDC Interim Guidance On Antiviral Chemoprophylaxis For Persons With Exposure To Avian Flu).


Despite the reassuring anecdotal data to date, it is important to understand the pathogenesis of this virus in birds and mammals, with an eye towards understanding how the threat may change over time.  


While humans have been so far unaffected, we have seen reports of dogs being infected with H5N8 (see MAFRA: H5N8 Antibodies Detected In South Korean Dogs (Again)).   The ability to infect canines does not automatically make it a human threat, but it does raise some concerns (see Study: Dogs As Potential `Mixing Vessels’ For Influenza).


Although not perfect, ferrets are considered a reasonable mammalian substitute for humans when testing respiratory viruses because their lung physiology is similar, and because they cough and sneeze when infected, very much as humans do.


All of which brings us to a new study (most of which, alas, is behind a pay wall) that looks at the pathogenesis of two Korean strains of H5N8 challenged ferrets.  What we can tell from the abstract, however, is that ferrets intranasally inoculated suffered no mortality or serious respiratory symptoms, but that ferrets intratracheally infected with one of the H5N8 strains showed `dose-dependent mortality’.


Pathogenesis of novel reassortant avian influenza virus A (H5N8) Isolates in the ferret 

Heui Man Kim1, 2, , Chi-Kyeong Kim1, 3, , Nam-Joo Lee, Hyuk Chu, Chun Kang, Kisoon Kim, Joo-Yeon Lee,



•  Outbreaks of HAPI H5N8 occurred in 2014, and spread to poultry farms in Korea.

• We evaluated the pathogenesis of H5N8 viruses in ferrets.

• Two Korean H5N8 strains did not induce mortality in intranasal challenged ferrets.


Outbreaks of avian influenza virus H5N8 first occurred in 2014, and spread to poultry farms in Korea. Although there was no report of human infection by this subtype, it has the potential to threaten human public health. Therefore, we evaluated the pathogenesis of H5N8 viruses in ferrets. Two representative Korean H5N8 strains did not induce mortality and significant respiratory signs after an intranasal challenge in ferrets. However, ferrets intratracheally infected with A/broiler duck/Korea/Buan2/2014 virus showed dose-dependent mortality. Although the Korean H5N8 strains were classified as the HPAI virus, possessing multiple basic amino acids in the cleavage site of the hemagglutinin sequence, they did not produce pathogenesis in ferrets challenged intranasally, similar to the natural infection route. These results could be useful for public health by providing the pathogenic characterization of H5N8 viruses.


While it isn’t easy to infect a ferret, apparently if you provide a high enough dose, and place it far enough down the respiratory tract, it is possible.  Whether these same (unlikely to occur) conditions would elicit the same response in humans is unknown, but it is possible.

Although it is tempting to relegate H5N8 to the `only a threat to poultry’ column, the simple fact is: viruses constantly change. 


We’ve already seen multiple strains, new clades, and additional reassortants (H5N2, H5N3, H5N1) emerge since the H5N8 virus first appeared in early 2014, and more are undoubtedly on the horizon.  How they will behave, and the threat they pose to humans, may change as well. 

For now,  the news remains good, at least in so far as human infection is concerned. 


For the poultry industry, however, there is considerably less to celebrate. 


H5N8 and it’s reassortant H5N2 progeny appear to spread faster, and more easily by wild and migratory birds than any HPAI virus previously observed.  It is highly pathogenic in chickens, turkeys, and ducks - and if Taiwan’s outbreak is any indication (875 farms & counting) - once it enters a region’s poultry population, it is capable of spreading with alarming speed. 

All of which means that H5N8 (and its descendents) have staying power, and are likely to be with us for some time.

1 comment:

Giga Gerard said...

I read somewhere that Ferrets have receptors for avian flu deep in the lungs, but not in the upper respiratory tract where airborne contamination occurs.