Thursday, May 11, 2017

Eurosurveillance: Biological Characterisation Of (HPAI) A(H7N9) Viruses In Humans


Credit FAO - May 10th Update

















#12,450


Earlier today in CHINA: HPAI H7N9 Expands Its Range we looked at how the recently emerged HPAI H7N9 virus has spread from Guangdong Province, to Fujian, Hunan, Guangxi, and Hebei Provinces.
Other than preliminary reports that this virus can infect humans, and that some cases displayed signs of antiviral resistance, we've seen precious little else about its behavior and the threat it may pose to humans. 
Today, the ECDC's Eurosurveillance Journal has published a Rapid Communications from scientists at China's CDC studying this new virus, and some of what they've discovered is less than comforting.

While there is a lot to absorb here, the upshot is this HPAI H7N9 virus retains the ability to infect both birds and humans, and in fact, appears to be potentially slightly more infectious in both than the LPAI version. The authors write:
Our data show that the HPAI H7N9 viruses retained dual receptor binding properties, with slightly increased binding preference for both receptors compared with LPAI H7N9 (AnH1) viruses. . . . .  The persisting preference for both avian- and human-type receptors of HPAI H7N9 viruses may result in their circulation in poultry and possible transmission among humans.
 
Influenza in humans (and other mammals) is primarily a respiratory disease.  Human adapted influenza viruses have an affinity to bind to the α2-6 receptor cells that line the upper airway and lungs in humans, and are spread via coughs and sneezes. 
Avian influenza viruses preferentially bind to the α2-3 receptor cells that are commonly found in the gastrointestinal tract of birds. While humans also have some α2-3 receptor cells, they are primarily found deep in the lungs. 
The ability of an avian virus to bind to both types of receptor cells is viewed as one of the most important hurdles it must cross in order to have genuine pandemic potential.  It isn't the only barrier, but it is certainly the biggest one. 
They also find that (as was hinted previously), this HPAI H7N9 virus can quickly mutate into an antiviral resistant virus during treatment.  This HPAI virus is also antigenically different from the older LPAI H7N9 virus, and so existing vaccines are unlikely to be effective.

Follow the link to read the full report, as I've only included some highlights below:

Eurosurveillance, Volume 22, Issue 19, 11 May 2017
Rapid communication
Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017

W Zhu 1 2 , J Zhou 1 2 , Z Li 1 2 , L Yang 1 , X Li 1 , W Huang 1 , S Zou 1 , W Chen 1 , H Wei 1 , J Tang 1 , L Liu 1 , J Dong 1 , D Wang 1 , Y Shu 1

Correspondence: Yuelong Shu (yshu@cnic.org.cn)


Citation style for this article: Zhu W, Zhou J, Li Z, Yang L, Li X, Huang W, Zou S, Chen W, Wei H, Tang J, Liu L, Dong J, Wang D, Shu Y. Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017. Euro Surveill. 2017;22(19):pii=30533. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.19.30533
Received:14 April 2017; Accepted:10 May 2017

With no or low virulence in poultry, avian influenza A(H7N9) virus has caused severe infections in humans. In the current fifth epidemic wave, a highly pathogenic avian influenza (HPAI) H7N9 virus emerged. The insertion of four amino acids (KRTA) at the haemagglutinin (HA) cleavage site enabled trypsin-independent infectivity of this virus. Although maintaining dual receptor-binding preference, its HA antigenicity was distinct from low-pathogenic avian influenza A(H7N9). The neuraminidase substitution R292K conferred a multidrug resistance phenotype.

Five outbreak waves have occurred since the low-pathogenic avian influenza A(H7N9) virus (LPAI H7N9) first emerged in spring 2013 in eastern China [1]. Highly pathogenic avian influenza A(H7N9) (HPAI H7N9) viruses, derived from their LPAI H7N9 counterparts, have recently been isolated from humans and resulted in fatal outcome in Guangdong, China (A/Guangdong/17SF003/2016 (SF003) and A/Guangdong/17SF006/2017 (SF006)) [2].
Both viruses contain an insertion of four amino acids (KRTA) in the haemagglutinin (HA) proteolytic cleavage site, indicating their pathotype switch from LPAI to HPAI. Furthermore, they retain a series of genetic features contributing to the ability to infect humans (e.g. 186V in the HA protein (H3 numbering) and 627K in the PB2 protein) that raise concerns regarding their pandemic potential.
Amino acid substitutions associated with resistance to neuraminidase inhibitors (NAIs) have been detected in both SF003 and SF006 viruses. Therefore, to update public health risk assessment, we investigated trypsin-dependent infectivity, receptor binding properties, antigenic alternations of the HPAI H7N9 viruses, as well as their sensitivity to antiviral drugs. All LPAI H7N9 viruses in this study were isolated from humans.
         (SNIP)

         DISCUSSION
DiscussionCompared with other avian influenza viruses, LPAI H7N9 and HPAI H5N1 are of most concern because of their high mortality and morbidity. LPAI H7N9 poses a higher risk for humans than HPAI H5N1 because LPAI H7N9 could bind sialic acid α2,6 human-type receptors while HPAI H5N1 could not.
Our data show that the HPAI H7N9 viruses retained dual receptor binding properties, with slightly increased binding preference for both receptors compared with LPAI H7N9 (AnH1) viruses. It is well known that human upper respiratory tissues and trachea contain mainly α2,6 receptors while lung tissue possesses mixtures of avian type α2,3 and human type α2,6 receptors [7,12]. The persisting preference for both avian- and human-type receptors of HPAI H7N9 viruses may result in their circulation in poultry and possible transmission among humans.

Vaccination is the primary measure to control the spread of influenza virus infection in humans. Previously, WHO recommended A/Anhui/1/2013 (LPAI H7N9) as the vaccine strain for influenza A(H7N9) virus. However, our data show that the newly emerged HPAI H7N9 viruses did not react strongly with the ferret antisera of LPAI H7N9 viruses. Therefore, WHO has recently recommended SF003 as an additional candidate vaccine virus.

Among the four commercially available NAIs, oseltamivir and zanamivir are the predominant NAIs for influenza prophylaxis and treatment [13]. Our results show that HPAI H7N9 viruses with the 292K amino acid in the NA protein exhibited multi-drug resistance. The viral neuraminidase could acquire the R292K substitution as early as 2 days after administration of the antiviral drug. Further assessment of the fitness of drug-resistant viruses is urgently needed.

In summary, although the highly pathogenic influenza A(H7N9) virus was thought to cause higher risk in poultry than the low-pathogenic virus, our study, especially regarding the receptor profile of HPAI H7N9 viruses, has implications on surveillance and control strategies not only in the animal sector but also for public health. Our study also highlighted the critical role of antiviral surveillance monitoring in the clinical management of influenza virus infection as an essential component of pandemic preparedness.


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