#17,918
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.
While other LPAI subtypes are not currently reportable to WOAH (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. H9N2 has repeatedly 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).
We've also seen spillovers of several other LPAI avian influenza viruses into humans - including LPAI H6N1 in Taiwan, LPAI H3N8 in China, LPAI H7N2 in NYC, LPAI H7N4 and several varieties of LPAI H10Nx, also in China.
The biggest impacts have come, however, from HPAI H5N1 (886 cases), LPAI & HPAI H7N9 (1568 cases) and HPAI H5N6 (90 cases).
As a result, we tend to focus primarily on H5 and H7 avian viruses, even though there are others that have zoonotic potential. From time to time, we've taken deeper looks at some of the less obvious threats, including:
Vet. Microb.: Detection Of Non-notifiable LPAI H4N6 In Poultry In Great Britain
Today we've a another report on LPAI H4N6, which is ubiquitous in wild birds both in Asia, and around the world, and which has previously shown signs of better adapting to mammalian hosts.
Today's study is both detailed and lengthy, so I've only posted some excerpts. Follow the link to read the report in its entirety. I'll have a bit more after the break.
Genetics and Pathogenicity of Influenza A (H4N6) Virus Isolated from Wild Birds in Jiangsu Province, China, 2023Xingdong Song,1Jingman Tian,2Minghui Li,2Xiaoli Bai,2Zhiguo Zhao,2Jianzhong Shi,2Xianying Zeng,2Guobin Tian,2Yuntao Guan,2Pengfei Cui,2Guohua Deng,2and Liling Liu2 et al.Show more
Published 14 Feb 2024
Abstract
During the routine surveillance, we isolated nine H4N6 subtype avian influenza viruses (AIVs) in Jiangsu Province, China, in March 2023. Phylogenetic analysis revealed that nine H4N6 viruses belonged to the Eurasian lineage and underwent complex genetic recombination among Asian countries during their evolution.
It is particularly noteworthy that the PB2 and PB1 genes of our representative virus were descended from clade 2.3.4.4b H5 high-pathogenic AIVs in Japan. Mutations of D3V and D622G in PB1, N66S in PB1-F2, N30D, I43M, and T215A in M1, and P42S and I106M in NS1 were observed in nine isolates, which may increase the pathogenicity of the viruses in mice.
The receptor binding analysis showed that the tested H4N6 virus could bind to both avian-type and human-type receptors. Vitro infection kinetics revealed that the representative virus could efficiently replicate in mammalian cells, including MDCK and 293T cells. Pathogenicity tests in mice indicated that the representative virus could replicate in nasal turbinates and lungs without prior adaptation. Our data reveal the potential public health issues represented by H4N6 viruses from wild birds and highlight the need to strengthen routine surveillance of wild birds.
(SNIP)
Although the H4 subtype AIV is classified as an LPAIV, it spreads widely in wild bird species worldwide, has been found in poultry [12–14], and can even infect mammals such as pigs [15–17]. Some studies have shown that the H4 AIVs can infect mice without any prior adaptation [12] and were efficiently transmitted among guinea pigs by direct contact [13]. In addition, H4 AIVs can bind to avian-like receptors (α−2,3-sialic acid receptors) and even acquire the ability to bind to human-like receptors (α−2,6-sialic acid receptors) [18]. Therefore, we should pay great attention to the public health concerns from the H4 viruses.
In this study, we isolated nine H4N6 subtype AIVs from mallards in Yancheng City, Jiangsu Province, China in March 2023, and we analyzed the phylogenetic evolution characteristics, receptor binding preference, replication capacity in vitro, and pathogenicity in mice of the H4N6 virus. Our data revealed that the H4N6 viruses posed a potential threat to public health security, and it is necessary to strengthen regular surveillance of the H4N6 viruses circulating in wild birds.
(SNIP)
The switch in receptor binding specificity from avian-type to human-type sialic acid receptors is an important mutation of AIVs, which is considered to be one of the major determinants of its efficient replication in human hosts [47]. In this study, the tested H4N6 virus isolated from wild birds exhibited dual receptor binding preferences, with a certain ability to bind to human-type receptors, which is similar to the receptor binding properties of H4 viruses isolated from domestic ducks [13]. However, whether the H4N6 viruses isolated from chickens also have dual receptor binding properties deserves further exploration. These data highlight the potential threat of H4N6 viruses to mammals.
Influenza A virus is prone to adaptive mutations during their evolution process to replicate efficiently in mammals [48]. In this study, nine H4N6 isolates contain the D3V and D622G mutations in the PB1 protein, N66S mutation in the PB1-F2 protein, N30D, I43M, and T215A mutations in the M1 protein, and P42S and I106 M mutations in NS1 protein, which may contribute to increased virulence of the viruses in mice.
To investigate the ability of the H4N6 virus isolated from wild birds to infect mammals, we conducted both in vitro and in vivo experiments. The results showed that the tested virus could replicate well in mammalian cells, including MDCK and 293T cells. Also, the tested virus acquired the ability to replicate in the mammalian model, the BALB/c mice, without prior adaptation. These data suggest that the H4N6 virus from wild birds acquired several mammalian adaptive mutations and could efficiently replicate in mammalian cells and mice, which posed a potential threat to public health security. Thus, we should continue to pay attention to whether the H4N6 virus will cross the interspecies barrier to infect humans.
5. Conclusions
In summary, the H4N6 viruses newly isolated from wild birds were recombinant from different subtypes of AIVs among Asian countries, especially their PB2 and PB1 segments derived from H5 HPAI viruses, and the genome possessed molecular signatures that enhanced the pathogenicity in mammals. Our data revealed that the representative H4N6 virus exhibited dual receptor binding properties and could be replicated both in mammalian cells, including MDCK and 293T cells, and in BALB/c mice. Therefore, we should focus on the public health concern represented by H4N6 viruses, and we propose that active monitoring of H4N6 viruses from wild birds s4.
The superpower of influenza viruses is its ability to reassort with other influenza viruses, and potentially gain new traits or increased biological `fitness'.
Six years ago, in Reassortment After Co-infection Of Chickens With H4N6 and H9N2 influenza Viruses - published in Veterinary Microbiology - we looked at a report that showed just how easily LPAI H4N6 reassorts with LPAI H9N2 in co-infected chickens, and that some of those reassortants showed signs of increased virulence.
The authors - including Chen Hualan, director of China's National Avian Influenza Reference Laboratory - wrote:Our results indicate that co-infection of an avian individual with the H4N6 and H9N2 viruses leads to a high frequency of reassortment and generates some reassortants that have higher virulence than the wild-type viruses in mammals.
These results highlight the potential public risk of the avian influenza reassortants and the importance of surveillance of the co-existence of the H4N6 and H9N2 viruses in avian species and other animals.
While H4N6 sits admittedly pretty far down on our pandemic worry list, the more we know about these non-notifiable LPAI viruses and their interactions with more worrisome subtypes, the less likely we are to be blindsided by an avian flu threat coming at us from out of left field.
