Wednesday, March 13, 2019

Two Studies On The Recent Evolution Of HPAI H5 Viruses In The Middle East

Credit Wikipedia


One of our biggest concerns about avian influenza is that these viruses are often found in regions of the world where surveillance and testing are marginal at best, or in places where press freedoms and government willingness to divulge information are less than exemplary (see Why No News Isn't Necessarily Good News).
The reasons behind these data deserts vary, with some due simply to a lack of resources, while others appear to be politically or ideologically driven. 
As the map above illustrates, the governments of China and much of the Middle East (including Northern Africa) tightly control the flow of information. To China's credit, however, they do publish an impressive number of highly detailed scientific papers, albeit often a year to two after-the-fact.
We tend to see fewer papers published from the Middle East, where H5N1, H5N8, and H9N2 all circulate (along with MERS-CoV).  Which means we don't have a very good handle on the evolutionary changes taking place in these viruses circulating in the region.
Today, however, we have two recent studies; one on the evolution of H5N1, and the other on changes to the H5N8. Both of which raise concerns.

Our first stop is Egypt, where over the summer of 2014, HPAI H5N1 picked up several key mutations (see Eurosurveillance: Emergence Of A Novel Cluster of H5N1 Clade which are believed to have helped increase its transmissibility from poultry to humans.
Six months later (spring 2015) we witnessed the largest human outbreak of H5N1 on record (see EID Dispatch: Increased Number Of Human H5N1 Infection – Egypt, 2014-15), with roughly 160 cases reported over five months.
The first (open access) study, which is published in Hosts and Viruses looks at changes in Egypt's H5N1 virus since that outbreak, and calls into question the effectiveness of Egypt's poultry vaccination program. Topics we've covered before (see Efficacy Of AI Vaccines Against The H5N8 Virus in Egypt and Egypt: A Paltry Poultry Vaccine).

I've only included some excerpts, so follow the link to read it in its entirety. 

Evolutionary Analysis and Phylodynamics of Avian Influenza Virus H5N1 between 2015 and 2016 in Egypt
Osama Elshazly 1 , AbdelSatar Arafa 1 , Mohammed A. Rohaim 2 , Ismaeil M. Reda 2 and Hussein A. Hussein 2*

Avian influenza viruses (AIVs) continue to pose global threats mainly due to their rapid evolving nature and the dynamic range of susceptible hosts. Zoonotic highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1 has recently diversified into two distinct genetic subclades ( and in Egypt.
This study was conducted as part of routine surveillance activities in Egypt; 5202 cloacal and oropharyngeal swabs were collected from live/dead birds, including commercial and backyard flocks, in five different locations in Egypt between the years of 2015 and 2016.
All samples were screened using virus isolation, as well as antigenic and molecular detection methods. Full-length hemagglutinin (HA) sequences of six representative H5N1 isolates were analysed to study their genetic evolution followed by estimation of their evolutionary rates among different virus clusters.
This analysis revealed a high evolution rate for clade Additionally, analysis of selection pressures in the HA gene revealed a positive selection pressure. Deduced amino acid analysis revealed characteristic mutations at HA antigenic sites besides two other mutations (129Δ, I151T) that were found to be stable in recent subclade isolates from humans and chickens.
Our results revealed that linking the epidemiological and sequence data is important to understand the prevalence, transmission, persistence and evolution of the virus, and to monitor the circulating AIV strains and emergence of new AIV subtypes in Egypt.
The wide circulation of the subclade, carrying triple mutations (120, 129Δ, I151T) associated with increased binding affinity to human receptors, is an alarming finding with public health importance.

Progressive evolution of the H5N1 viruses may have occurred in some governorates where multiple clades of viruses have circulated in different years. However, the small number of positive samples from these governorates does not provide strong evidence to support such homogeneity.

The fact that outbreaks continue to be reported, despite the widely practised vaccination against HPAI H5N1 virus, casts doubt on the effectiveness of the practise in Egypt. Inadequate vaccination coverage and improper application may have contributed to the observed vaccination ineffectiveness.

Strategically, quality-assured vaccines should be selected and used in high-risk areas against circulating strains and with consideration for the ease of applications as previous reports described that poor-quality vaccines have led to disease outbreaks (Peyre et al., 2009; FAO, 2011).

In conclusion, a new H5N1 cluster carries signatures from both chicken and human-adapted subclade has been identified. While genetic and biological characterizations were carried out in this study, further research is warranted to investigate the transmission potential of these viruses and to prevent the spread of human-adapted strains in Egypt. Additionally, mutations demonstrated here with unknown biological functions require further investigation.
        (Continue . . . .)

Adding to Egypt's H5 concerns, while details remain scant, last week we learned of a new, reassorted H5N2 virus (presumably a hybrid of either H5N1 & H9N2, or H5N8 & H9N2) in Egypt (see Egypt's OIE Notification Of A Reassorted HPAI H5N2 Virus).

Unlike H5N1, the H5N8 virus - which has spread faster and farther than any other HPAI H5 virus on record - has yet to cause a known human infection.  Instead, it has ravaged poultry flocks across Europe, Asia, North America, and the Middle East.

There have been studies, however, suggesting that H5N8 could someday acquire the ability to infect a wider range of hosts, including humans.  A few past blogs on this topic include:
Virology: The Zoonotic Potential Of Multiple Subgroups of Clade H5N8 Virus
J Vet Sci: Evolution, Global Spread, And Pathogenicity Of HPAI H5Nx Clade
Study: Virulence Of HPAI H5N8 Enhanced By 2 Amino Acid Substitutions

Sci Rpts: H5N8 - Rapid Acquisition of Virulence Markers After Serial Passage In Mice
To this list, we can add the following (abstract only) report published by Comparative Immunology, Microbiology and Infectious Diseases, on the full genomic characterization of an H5N8 virus isolated from a crow in Iran.  As we've seen previously, clade H5 reassorts easily with other viruses, and continues to pick up signs of mammalian adaptation.

Full genome characterization of Iranian H5N8 highly pathogenic avian influenza virus from Hooded Crow (Corvus cornix), 2017: The first report


  • Identification of H5N8 highly Pathogen Avian Influenza Virus from Hooded crow (Corvus cornix) in a national park located at Esfehan province in Iran.
  • Based on HA sequencing results, it belongs to clade, and the cleavage site is (PLREKRRKR/G).
  • Complete genome characterization of this virus revealed probable reassortment of the virus with East-Asian low-pathogenic influenza viruses.
  • A mutation at antibody binding site of hemagglutinin A201E of Aghakhan revealed the probable initialization for antigenic drift of this virus.
  • Phenotypic markers related to the increased potential for transmission and pathogenicity to mammals were observed.

During 2014–2017 Clade H5N8 highly pathogenic avian influenza viruses (HPAIVs) have spread worldwide. In 2016, an epidemic of HPAIV H5N8 in Iran caused mass deaths among wild birds, and several commercial poultry farms and captive bird holdings were affected and continue to experience problems. Several outbreaks were reported in 2017. One of them is related to Hooded crow (Corvus cornix) in a national park in Esfahan province in 2017.
Whole genome sequencing and characterization have been done on the detected H5N8 sample. Based on HA sequencing results, it belongs to clade, and the cleavage site is (PLREKRRKR/G). Phylogenetic analysis of the HA gene showed that the Iran 2017 H5N8 virus clustered within subgroup Russia 2016 b of group B in H5 clade HPAIV.

On the other hand, the NA gene of the virus is placed in group C of Eurasian lineage. Complete genome characterization of this virus revealed probable reassortment of the virus with East-Asian low-pathogenic influenza viruses. Furthermore, the virus possessed some phenotypic markers related to the increased potential for transmission and pathogenicity to mammals at internal segments. This study is the first full genome characterization H5N8 HPAIV in Iran. The data complete the puzzle of molecular epidemiology of H5N8 HPAIV in Iran and the region.
Our study provides evidence for fast and continuing reassortment of H5 clade viruses, that might lead to changes in virus structural and functional characteristics such as the route and method of transmission of the virus and virus infective, pathogenic and zoonotic potential.
        (Continue . . . )

While reports of HPAI H5 in poultry and wild birds have been subdued of late, and we've seen very few H5 infected humans over the past two years, this reminds us that the evolutionary process continues around the globe. 
The reality is and that any of these viruses - or their offspring - could come back with a vengeance in the future.
Just one of the many reason's why pandemic preparations must continue (see WHO Global Influenza Strategy 2019-2030).

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