Nature: Evolution & Pathogenicity of H6 Avian Influenza Viruses, Southern China 2011-2017

#15,585

There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza).

• LPAI viruses are common in wild birds, cause little illness, and only rarely death.  They are not considered to be a serious health to public health (LPAI H7N9 being the exception). The concern is (particularly with H5 & H7 strains) that LPAI viruses have the potential to mutate into HPAI strains. 

• HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry, and can sometimes infect humans with serious result. Again, H5 and H7 viruses are of greatest concern, but other subtypes have also caused human illness and large poultry losses. 

Until the first decade of the 21st century, there was no uniform requirement to report or track LPAI infections. That changed in 2006 when the OIE made reporting of LPAI H5 & H7 viruses mandatory.

While other LPAI subtypes are not currently reportable to the OIE (see Terrestrial Animal Code Article 10.4.1.), that doesn't make them entirely benign.

The most obvious, and worrisome loophole is for LPAI H9N2, which is common in Asia and the Middle East, and has recently moved into Africa. While not a notifiable virus, H9N2 has demonstrated its ability to infect humans and to reassort with other viruses, and is on the CDC's short list of novel viruses with pandemic potential (see CDC IRAT Score).

But H9N2 is not alone. 

One of the other low-profile and little watched zoonotic contenders are H6 viruses, which are common in both wild birds globally and domesticated poultry in China, and have demonstrated the ability to jump species (to humans, to pigs, and to dogs) as well. 

• In 2013, LPAI H6N1 was identified as the cause of pneumonia in a human  in Taiwan. The patient, a 20-year-old female, was hospitalized with mild pneumonia on May 8th, treated with oseltamivir (Tamiflu ®), and released from the hospital on May 11th.

• The following year, we learned that H6N1 had jumped to Taiwanese dogs (see Taiwan: Debating The Importance Of H6N1 In Dogs).

• In 2015's EID Journal: Seropositivity For H6 Influenza Viruses In China, researchers found a a small, but significant number of people in their survey who tested positive for H6 influenza antibodies (indicating previous exposure).

• Also in 2015, in Study: Adaptation Of H6N1 From Avian To Human Receptor-Binding, we saw a report citing changes the authors suggest are slowly moving the H6N1 virus towards preferential binding to human receptor cells instead of avian receptor cells

• LPAI H6N6 emerged in Chinese swine more than a decade ago (see Pathogenicity and transmission of a swine influenza A(H6N6) virus),  and continues to show signs of adaptation to mammalian hosts (see Trans. Emerg, Dis: Continued Reassortment of Avian H6 viruses - Southern China, 2014-2016.)

• In 2018, in Infect. Gen. Evol.: Emergence Of Novel Reassortant H6N2 Avian Influenza Viruses In Ducks In India, researchers isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively. 

• Last December, in BMC Vet. Rsrch.: Continuing Evolution of H6N2 Influenza A Virus in South Africa, we looked at evolution of H6N2 viruses in South Africa which, according to the authors, may have zoonotic potential. 

• Even Europe isn't exempt, as a year ago today in Netherlands: Multiple Farms Report LPAI H6, we looked at an unusual outbreak of LPAI H6 in poultry farms in the Netherlands. 

But since H6 viruses only rarely produce clinical illness in poultry, and are not legally reportable to the OIE, we are only rarely aware of their presence, or of the potential threat they may pose. 

All of which serves as prelude to a new study, published yesterday in Nature Scientific Reports, that looks at the evolution of H6 viruses in China, and their growing adaptation to mammalian physiology. 

It's a detailed and lengthy open-access report, so I've only reproduced the abstract. Follow the link to read it in its entirety.  I'll have a brief postscript when you return. 

Evolution and pathogenicity of H6 avian influenza viruses isolated from Southern China during 2011 to 2017 in mice and chickens

Weishan Lin, Hongrui Cui, Qiaoyang Teng, Luzhao Li, Ying Shi, Xuesong Li, Jianmei Yang, Qinfang Liu, Junliang Deng & Zejun Li

Scientific Reports volume 10, Article number: 20583 (2020) Cite this article

Abstract

H6 subtype avian influenza viruses spread widely in birds and pose potential threats to poultry and mammals, even to human beings. In this study, the evolution and pathogenicity of H6 AIVs isolated in live poultry markets from 2011 to 2017 were investigated. 

These H6 isolates were reassortant with other subtypes of influenza virus with increasing genomic diversity. However, no predominant genotype was found during this period. All of the H6N2 and most of the H6N6 isolates replicated efficiently in lungs of inoculated mice without prior adaptation.

 All of the H6N2 and two H6N6 isolates replicated efficiently in nasal turbinates of inoculated mice, which suggested the H6N2 viruses were more adaptive to the upper respiratory tract of mice than the H6N6 viruses. 

One of H6N2 virus caused systemic infection in one out of three inoculated mice, which indicated that H6 avian influenza virus, especially the H6N2 viruses posed a potential threat to mammals. Five H6 strains selected from different genotypes caused no clinical signs to inoculated chickens, and their replication were limited in chickens since the viruses have been detected only from a few tissues or swabs at low titers. 

Our study strongly suggests that the H6 avian influenza virus isolated from live poultry markets pose potential threat to mammals.

          (Continue . . . )

 
The conventional wisdom is that H6 viruses are unlikely to pose a serious zoonotic threat, but eight years ago LPAI H7 viruses were also thought to be a weak cousin of HPAI H5N1, and incapable of producing the same level of virulence or spread in humans.

The emergence of LPAI H7N9 in China in 2013 - sporting a mortality rate (among those hospitalized) of 30% - has dispelled that notion. A severe human infection with LPAI H7N4 in China in 2018 showed this was not a fluke.

Admittedly, H6 sits pretty low on our novel flu worry list, but the more we know about these non-notifiable LPAI viruses, the less likely we are to be blindsided by a pandemic threat coming at us from out of left field.