Credit CDC
#17,496
Although we often call influenza viruses only by their subtype (e.g. H5N1), that is really more of a nickname than a proper identifier. It only generally describes the virus, as there can be scores of similarly designated viruses with substantially different genetics and properties.
When we talk about a subtype, however, we are really talking about a broad, often expanding array, of related viruses that share the same (or similar) HA and NA genes.
Within each HA subtype there are genetic groupings called clades (based on the lineage of the HA gene). Clades are often further divided into subclades. H5N1 started with clade 0 back in 1996, but has since expanded into dozens of clades and subclades, many of which flourished briefly but have since disappeared.
So far, the most successful H5 clade has been 2.3.4.4, which first gained notoriety nearly a decade ago as an H5N8 virus which decimated South Korea's poultry industry. This clade, via a circuitous route which involved numerous reassortments across several continents, has now evolved into 8 different subclades (A-H).
Of these, H5N1 clade 2.3.4.4b is currently the most widely reported around the world, but even within this narrow designation there are scores of genotypes (based on the makeup of its internal genes), and each of these can have minor variants (e.g. PB2-D701N, PB2-Q591K, PB2-E627K, etc) that can alter the behavior - and even the host range - of the virus.
With all of this genetic diversity within a single subtype, it is understandable that we'd see differences in transmissibility and pathogenicity as well. The mutability of HPAI H5 viruses explains why we are seeing increasing spillovers into mammalian wildlife, and why we are concerned over its pandemic potential.
Throughout the past 25+ years, the one constant with HPAI H5 viruses has been it has been highly transmissible, and nearly 100% fatal in poultry. To varying degrees, other bird species - particularly ducks - tolerate infection much better, which has allowed the virus to spread in the wild.
But as the following report from Emerging Microbes and Infections describes, HPAI H5N1 clade 2.3.4.4b appears to be losing some of its transmissibility in poultry. While some poultry farmers might consider that a `good thing', it may complicate detection and eradication efforts, and it may not end up being permanent.
The link, abstract, and some excerpts from the report follow, after which I'll have a brief postscript.
Research Article
Diverse infectivity, transmissibility, and pathobiology of clade 2.3.4.4 H5Nx highly pathogenic avian influenza viruses in chickens
Jung-Hoon Kwon,Kateri Bertran,Dong-Hun Lee,Miria Ferreira Criado,Lindsay Killmaster,Mary J. Pantin-Jackwood & David E. Swayne
Article: 2218945 | Received 13 Feb 2023, Accepted 23 May 2023, Published online: 12 Jun 2023
Download citation https://doi.org/10.1080/22221751.2023.2218945
ABSTRACT
Clade 2.3.4.4 Eurasian lineage H5Nx highly pathogenic avian influenza virus (HPAIV) has become the globally dominant clade and caused global outbreaks since 2014. The clade 2.3.4.4 viruses have evolved into eight hemagglutinin subgroups (2.3.4.4a-h).
In this study, we evaluated the infectivity, pathobiology, and transmissibility of seven clade 2.3.4.4 viruses (two 2.3.4.4a, two 2.3.4.4b, one 2.3.4.4c and two 2.3.4.4e) in chickens. The two clade 2.3.4.4e viruses caused 100% mortality and transmissibility in chickens. However, clade 2.3.4.4a and c viruses showed 80–90% mortality and 67% transmissibility.
Clade 2.3.4.4b viruses showed 100% mortality, but no transmission to co-housed chickens was observed based on lack of seroconversion.
All the infected chickens died showing systemic infection, irrespective of subgroup. The results highlight that all the clade 2.3.4.4 HPAIVs used in this study caused high mortality in infected chickens, but the transmissibility of the viruses in chickens was variable in contrast to that of previous Eurasian-lineage H5N1 HPAIVs. Changes in the pathogenicity and transmissibility of clade 2.3.4.4 HPAIVs warrant careful monitoring of the viruses to establish effective control strategies.
(SNIP)
The clade 2.3.4.4 viruses are continuously evolving into multiple genotypes by reassortment with prevailing LPAIVs in wild birds [6,12, 13,15,16,43]. Although the clade 2.3.4.4e viruses showed higher mortality and transmissibility than other viruses in this study, the pathogenicity of a specific virus can be readily changed by further reassortment with other viruses. Therefore, the biological characteristics of newly emerging genotypes should be continuously monitored to inform veterinary authorities of any increases in adaptation to poultry and thus an increased risk of transmission.
Clade 2.3.4.4 H5Nx HPAIVs have become the dominant clade in wild birds since 2014, especially the clade 2.3.4.4b HPAIVs which have caused global outbreaks in Asia, Europe, Africa, and America [C4,8,10,14–18,43–45].
The relatively low infectivity and transmissibility of some clade 2.3.4.4 H5Nx viruses for chickens, especially broiler chickens, compared to previous Gs/GD-lineage H5N1 HPAIVs may delay and hinder rapid, accurate diagnoses on farms and may limit early disease control. Sharing updated pathogenicity information with field veterinarians and poultry farmers will be crucial for the early detection and control of HPAIVs.
During the 2016–2017 clade 2.3.4.4b HPAIV epizootic in Europe, most poultry cases were detected in domestic waterfowl, including ducks and geese, and outbreaks were focused in high duck density areas such as France and Hungary [46]. In South Korea, domestic ducks played a central role in the clade 2.3.4.4c H5N8 outbreak of 2014–2016; however, clade 2.3.4.4e H5N6 outbreaks occurred mostly in chickens [47,48].
Our results showed that clade 2.3.4.4e H5N6 viruses caused higher mortality and transmissibility than other clade 2.3.4.4 viruses in chickens, in line with field observations where clade 2.3.4.4e viruses predominated in chicken premises. Understanding the pathogenicity and susceptibility of poultry species to novel HPAIVs is a key to predicting disease outbreak patterns and establishing targeted control strategies.
We identified different levels of infectivity and transmissibility rates, and pathobiology of clade 2.3.4.4 H5Nx subgroups. In contrast to previous H5N1 HPAIVs of the Gs/GD lineage, clade 2.3.4.4 H5Nx HPAIVs continuously cause infection in wild birds and poultry, and evolve by reassortment with diverse LPAIVs in wild birds which can result in changes in pathobiology of viruses [12,15,41]. The evolution of HPAIVs and changes in their biological characteristics need to be continuously monitored for the effective control of HPAIV outbreaks.
The take-away here is that HPAI H5 has a lot of moving parts, many of which we only partially understand (or even recognize). The world faces not a lone viral threat, but literally dozens - maybe hundreds - all following different evolutionary paths.
Most will be evolutionary failures, and fade away just as hundreds of other variants have done in the past. But it only takes one lucky virus to stumble upon the right combination of genetic changes to ruin our whole day.
Add in the fact that HPAI is far from the only threat out there, and our current inter-pandemic period may prove short-lived. Good reasons why we need to be preparing for the next pandemic threat with a sense of urgency.
The following quote is nearly 20 years old, but it is just as true today as it was in 2006:
“Everything you say in advance of a pandemic seems alarmist. Anything you’ve done after it starts is inadequate." - Michael Leavitt, Former Secretary of HHS
