Monday, November 28, 2016

Korea: H5N6 A New Reassortant Virus - MAFRA


Korea's Ministry of Agriculture (MAFRA) today released a preliminary genetic analysis of four recently obtained H5N6 virus samples from South Korea, and compares them to the same virus subtypes collected previously from Mainland China and Hong Kong
What they found is that the Korean H5N6 virus has changed internally from its predecessors, and that - as we've seen previously - its genetic evolution continues.

Like all influenza viruses, avian H5N6 is constantly changing.  This evolution is driven by two different processes. Antigenic drift & Antigenic Shift (reassortment).
  • Antigenic drift causes small, incremental changes in the virus over time. Drift is the standard evolutionary process of influenza viruses, and often come about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift).
  • Shift occurs when one virus swap out chunks of their genetic code with gene segments from another virus. This is known as reassortment. While far less common than drift, shift can sometimes produce abrupt, dramatic changes to the virus (see NIAID Video: How Influenza Pandemics Occur).
Six months ago, in EID Journal: Novel Reassortant H5N6 Viruses In Humans, Guangdong China, we looked at an analysis of 3 viruses collected last December in Guangdong Province, which found H5N6 had reassorted with both H9N2 and H6N6 since it emerged in 2014.

Two of the three isolates examined also appear to have picked up genes for amantadine (an older antiviral) resistance, that were not present in 2014.

The authors suggested there may be other - as yet undetected - H5N6 reassortants in the wild and others may yet emerge.

Today's announcement indicates that while Korea's H5N6 HA and NA genes are roughly a 99% match to earlier samples, some if its internal genes have changed - likely through reassortment - and at least one (PA gene) is only about a 92% match to previous samples. 

Exactly how these genetic changes might affect the behavior of the virus (if at all) isn't yet known, although Korea's CDC is conducting tests to determine its potential pathogenicity in humans. 

It seems likely that the virus picked up these changes as it circulated among birds in their summer breeding areas of Siberia and Northern China, a process we looked at last August in Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1.

First the (translated) report, then I'll return with a bit more.

H5N6 type AI virus gene analysis Intermediate results 

Entry date 2016-11-28 14:00:00

□ Genetic analysis of 4 cases of highly pathogenic AI (H5N6) virus in Korea,
* Cheonan wild bird feces, Iksan Mangyeong River white cheek duck, Haenam laying hen,
○ It was analyzed as similar to H5N6 virus which was popular in Guangdong province, Hong Kong, China
- H5 and N6 genes have the highest homology with the virus isolated from Hong Kong wild bird
* H5 gene (98.94-99.24%), N6 gene (99.06-99.13%) However, the four isolated viruses differ from each other in some internal genes.
* H5, 6 genes (over 99%), PA gene (91.77-99.81%), NS gene (96.84-99.64%),

○ Domestic isolation When compared with the H5N6 virus, which was prevalent in Guangdong province, Hong Kong and China, one of the internal genes was analyzed to be a low-pathogenic AI virus gene in wild birds,

- It is presumed that the virus is generated by recombination of Chinese H5N6 virus and low-pathogenic AI virus in wild birds,
- The process of recombination seems to have been made in the course of the arrival of wild birds infected with H5N6 in China, Guangdong Province and Hong Kong to breeding sites in Siberia and northeastern China,

□ We plan to continue the genetic analysis and pathogenicity investigation of additional AI viruses in the future.
□ In order to evaluate the harmfulness of the influenza H5N6 virus, the virus was provided to the Disease Control Headquarters of the Ministry of Health and Welfare on November 24, and the disease management headquarters will conduct an analysis on the human health risks.

Clade viruses (which include both H5N8 and H5N6) have demonstrated an enhanced ability to reassort with other - mostly LPAI - viruses, and continue to evolve and occasionally churn out viable novel subtypes.

A recent study published in the Journal Science, called the Role for migratory wild birds in the global spread of avian influenza H5N8, stated:

Further, we found that the hemagglutinin of clade virus was remarkably promiscuous, creating reassortants with multiple neuraminidase subtypes.
We looked at one possible explanation for these changes early last week in EID Journal: HPAI A(H5Nx) Viruses With Altered H5 Receptor-Binding Specificity, where researchers suggested:

`Altered receptor-binding properties might affect the balance between HA and NA, enable the virus to acquire different NA subtypes, and might result in altered host range and spreading.'

Regardless of the exact mechanism behind it, the genetic makeup of H5N6 clade continues to evolve (see Continuing Reassortant of H5N6 Subtype Highly Pathogenic Avian Influenza Virus in Guangdong), making it a particularly unpredictable foe.

We will hopefully see additional, and more detailed, genetic analysis of Korea's H5N6 virus in the days to come.

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