Thursday, February 22, 2018

WHO: Genetic Characteristics Of Avian H7N4

Credit CDC











 







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Eight days ago, in Jiangsu China Reports 1st Novel H7N4 Human Infection, China announced the first known human infection with avian H7N4 which resulted in a 3-week hospitalization for a 68 year old woman in Jiangsu Province for severe pneumonia.

While human infection with avian H7 viruses hasn't been unheard of, until H7N9 emerged in China in 2013, they were fairly rare and almost always mild.  A few examples include:
After the wake up call from H7N9, when a severe human infection with a novel H7N4 virus is reported from China, we naturally take notice.

Today, in addition to releasing their Recommended Composition Of 2018-2019 Northern Hemisphere Flu Vaccine, the World Health Organization has released a new Antigenic and genetic characteristics of zoonotic influenza viruses report for February 2018.

Included is the following excerpt on the recently reported H7N4 virus, which shows that this virus is a purely avian LPAI H7 strain - distinct from A(H7N9) - although it carries the PB2  637K marker associated with mammalian adaptation.
Researchers have determined the (E627K) substitution in the (PB2) protein - the swapping out of the amino acid Glutamic acid (E) at position 627 for Lysine (K) - makes the an influenza virus better able to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract (see Eurosurveillance: Genetic Analysis Of Novel H7N9 Virus).
Although the virus was not isolated (only detected by RT-PCR) in the patient, it was isolated from contact poultry.  A brief excerpt (bolding mine) from today's report:

Antigenic and genetic characteristics of zoonotic influenza viruses and candidate vaccine viruses developed for potential use in human vaccines

(EXCERPT)

Influenza A(H7N4)

Influenza A(H7N4) activity from 26 September 2017 to 19 February 2018
The first human case of influenza A(H7N4) virus infection was reported by China. The case was from Jiangsu province, and the individual developed severe pneumonia and survived. The throat swab collected from the patient tested positive for A(H7N4) by real-time RT-PCR and sequencing. The individual had slaughtered chickens prior to illness onset and LPAI A(H7N4) viruses were detected in ducks and chickens on the premises. None of the close contacts of the infected individual reported symptoms and all tested negative for influenza.

Genetic characteristics of the influenza A(H7N4) virus

 
Viral gene sequence analysis generated from clinical material showed that all segments of the human virus shared high identity with wild bird avian influenza viruses. The HA gene was distinct from the A(H7N9) viruses circulating in China and was characterised as low pathogenicity by HA cleavage site sequence. No mutations associated with reduced susceptibility to neuraminidase inhibitors, amantadine or rimantadine, were found. The PB2 carried the 627K marker associated with mammalian adaptation. Virus has not been isolated from the infected individual.


Influenza A(H7) candidate vaccine viruses

 
Based on the current antigenic, genetic and epidemiologic data, no new CVVs are proposed. The available A(H7) CVVs, excluding A(H7N9) CVVs listed above, are listed in Table 6.
       
http://www.who.int/influenza/vaccines/virus/201802_zoonotic_vaccinevirusupdate.pdf?ua=1



Whether this is a one-off event, or the first hint of a new emerging threat, is impossible to say.  But the fact that this isn't a reassortment of the already endemic, and highly dangerous H7N9 virus is probably a good sign.