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H5N1 genetic sequences - 2024+


Tom Peacock
@PeacockFlu
·
36m


A reminder that, although there is a (probably heavily human-assisted) mammal to mammal in the American cows, theres whats probably respiratory mammal to mammal transmission throughout the whole of South America in seals/sealions thats been going on for over a year now...

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bioRxiv Microbiology
@biorxiv_micrbio
·
19h
Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal ... https://biorxiv.org/cgi/content/short/2024.05.31.596774v1… #biorxiv_micrbio


​
 
Also commented by:


Roland Baker

@RolandBakerIII
·
1h


Phylogenetic data support mammal-to-mammal transmission of H5N1 & Adaptation Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal transmission

biorxiv.org
Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased...
H5N1 high pathogenicity avian influenza (HPAI) viruses of the clade 2.3.4.4b have killed thousands of marine mammals in South America since 2022. In October 2023, following outbreaks in sea lions in...


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Roland Baker

@RolandBakerIII
·
1h


SNPs specific to the marine mammal clade: * Q591K and D701N in PB2 * L548F in PB1 * A20T, M86I, and M548I in PA * R21Q and I226T in NS1


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Roland Baker

@RolandBakerIII
·
58m


"We believe that the high mortality rate in elephant seal pups is also consistent with mammal-to-mammal transmission, as pups are toothless and nurtured exclusively through nursing from their mothers."


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Roland Baker

@RolandBakerIII
·
57m


"Some newborns may have been infected before birth, as transplacental transmission of H5N1 HPAI viruses has been reported in humans and high virus loads were detected in aborted sea lion fetuses."


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Roland Baker

@RolandBakerIII
·
51m


"Mammal-to-mammal transmission is also supported by our regional phylogenetic analysis, which identified a novel H5N1 2.3.4.4b clade with viruses that appear to be specific to marine mammals. This marine mammal clade comprises strains with mutations..."


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Roland Baker

@RolandBakerIII
·
51m


"...that were not present in H5N1 2.3.4.4b viruses in birds (wild and domestic) from Peru, Chile, Argentina, Uruguay and Brazil, excepting occasional spillovers from marine mammals to coastal birds (terns and sanderling)."


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Roland Baker

@RolandBakerIII
·
48m


They authors note that ecologically it is unlikely adults are getting H5N1 infections via food sources or interactions with birds. South American sea lions regularly visit multiple rookeries and haul-outs and likely spread H5N1 directly throughout Venezuela, Uruguay and Brazil.


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Roland Baker

@RolandBakerIII
·
46m


Some of these mutations (such as Q591K and D701N in PB2) are associated with increased virulence, transmission, or adaptation to mammalian hosts and have been maintained since they first emerged in H5N1 HPAI viruses in marine mammals in Chile.


​more....
 
More from the study posted above:
...
Within the Americas branches, the cattle derived H5N1viruses form a distinct group within the 2.3.4.4b clade (Fig. 1). The new group shows a cluster of H5N1 strains isolated from various hosts in the United States in 2024, including dairy cows, domestic cats, raccoons, skunks, mountain lions, and several bird species. The clustering of sequences from the recent dairy cow outbreak indicates a common ancestor and suggests a potential transmission link between these species. Together, these data demonstrate that the recent outbreak of H5N1 in dairy cows is distinct from other circulating 2.3.4.4b H5N1 viruses.
...
H5N1 viruses circulating in the Americas have acquired mutations near the RBS

Several mutations have arisen in 2.3.4.4b viruses since 2022, particularly at L111M, T199I, and V214A (Fig. 3A). Notably, these three mutations lie outside of the traditional RBS, which is comprised of the 130-loop, 190-helix, and 220-loop23 143 . Analysis of these mutations based on location and outbreak revealed that all three mutations are specific to H5N1 viruses in the Americas (Fig. 3B). Importantly, we observed T199I was found in all H5N1 viruses from the dairy cow outbreak, as well as some H5N1 viruses circulating in the Americas not related to the ongoing dairy cow outbreak (Fig. 3B)...
We observed that the T199I mutation arose in the second half of 2023, with I199 becoming dominate by November 2023 (Fig. 3D-E). Notably, A/Texas/37/2024 HA NT sequence clusters more closely with an HA sequence collected from a mountain lion, also known as a cougar (Puma concolor) in Montana than sequences related to the ongoing dairy outbreak (Fig. 3E). Interestingly, the mountain lion isolate was collected in January 2024 and it was recently proposed that the dairy cow outbreak has been ongoing since late 2023 .. These data would suggest a closely related common ancestor from the mountain lion case to the ongoing dairy cow outbreak. Together, these data show that H5N1 viruses in the Americas have accumulated mutations within the RBS, with T199I being the only mutation specific to the ongoing dairy cow outbreak.
...
Our glycan binding data shows that 2.3.4.4b H5N1 viruses, including those related to the ongoing dairy cow outbreak, have not gained binding to α2,6 sialic acids, the most abundant human receptor for influenza viruses, despite the presence of α2,6 sialic acids within the cow mammary glands17,18 220 .​...
 
According to APHIS, a mountain lion collected on January 30, 2024 in Granite County was confirmed positive for EA H5N1 on February 27, 2024.

Detections of Highly Pathogenic Avian Influenza in Mammals
...
state county date_collected date_detected hpai_strain species

Montana Gallatin 2022-10-20 2022-10-28 EA H5N1 Skunk (unidentified)
Montana Madison 2022-11-22 2022-12-02 EA H5N1 Red fox
Montana Teton 2022-10-31 2022-12-06 EA/AM H5N1 Grizzly bear
Montana Flathead 2022-12-16 2022-12-20 EA/AM H5N1 Grizzly bear
Montana Cascade 2022-12-16 2022-12-20 EA H5N1 Striped skunk
Montana Sanders 2023-02-09 2023-02-22 EA H5N1 Raccoon
Montana Lake 2023-02-28 2023-03-08 EA/AM H5N1 Raccoon
Montana Custer 2023-02-28 2023-03-13 EA/AM H5N1 Striped skunk
Montana Custer 2023-02-28 2023-03-13 EA/AM H5N1 Striped skunk
Montana Park 2023-03-14 2023-03-17 EA H5N1 Striped skunk
Montana Gallatin 2023-03-17 2023-03-23 EA/AM H5N1 Striped skunk
Montana Madison 2023-04-14 2023-04-20 EA/AM H5N1 Mountain lion
Montana Rosebud 2023-04-13 2023-04-20 EA/AM H5N1 Striped skunk
Montana Mineral 2023-04-25 2023-08-04 EA/AM H5N1 Mountain lion
Montana Granite 2024-01-30 2024-02-27 EA H5N1 Mountain lion
Montana Yellowstone 2024-03-19 2024-04-26 EA/AM H5N1 Domestic cat

https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/mammals
 
Excerpt from the WOAH report:
...
PREVIOUSLY REPORTED OUTBREAKS
...
OB_132896 - GRANITE COUNTY
...
START DATE
2024/01/30
...
FIRST ADMINISTRATIVE DIVISION
Montana
...
LOCATION
Granite County
...
AFFECTED POPULATION DESCRIPTION
Wild mountain lion (Puma concolor). Samples were collected from a sub-adult female found dead.
...
https://wahis.woah.org/#/in-review/4451
 
Raj Rajnarayanan
@RajlabN
·
3m


#H5N1 updates PB2 of the house mouse sequences contain the recent “cattle outbreak adaptation signature” M631L H/T
@nextstrain
Special thanks to Karthik and Praneeth & Anderson Lab
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Nextstrain
@nextstrain
·
55m
Image
Replying to @0bFuSc8 @USDA_APHIS and 2 others
Thanks to quick work by Karthik G and Praneeth G to update SRA assemblies at https://github.com/andersen-lab/avian-influenza/…, we now have house mouse sequences up at the live site at https://nextstrain.org/avian-flu/h5...02/2024,A/House-Mouse/USA/24-014782-003/2024…


​
 
Raj Rajnarayanan
@RajlabN


#H5N1 #AvianFlu updates Quick Analysis of the sequence of H5N1 (clade 2.3.4.4b) #Colorado human case uploaded to
@GISAID
PB2 mutations: T58A, V109I, V139I, E249G, E362G, K389R, D441N, V478I, V495I, M631L*, V649I, M676A * Dairy cattle outbreak signature 1/n​

Raj Rajnarayanan
@RajlabN
·
11h


Sequence uploaded from Colorado contains unique PB2 E249G & NS1 R21Q mentioned in Singh et al. Detection and characterization of H5N1 HPAIV in environmental samples from a dairy farm. Virus Genes (2024) https://link.springer.com/article/10.1007/s11262-024-02085-4… 2/n
Content cover image
Detection and characterization of H5N1 HPAIV in environmental samples from a dairy farm
From link.springer.com


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Raj Rajnarayanan
@RajlabN
·
10h


Big thanks to all the associated laboratories from sample collection to sequence submission Awaiting Chicken sequences! 3/n


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Raj Rajnarayanan
@RajlabN
·
7h


Summary of HA mutations 4/n
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Raj Rajnarayanan
@RajlabN
·
7h


Summary of NA mutations 5/n
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Tom Peacock
@PeacockFlu
·
Jul 16


suggests the US have created a new reservoir of H5N1 that can keep spilling over into poultry all year round. Also these cattle viruses are partially mammalian-adapted which makes them better at jumping into people than normal poultry H5N1 - poultry can act as amplifying hosts​
 

Louise Moncla
@LouiseHMoncla


We've updated http://nextstrain.org/avian-flu with the human H5N1 sequence from Missouri, viewable at https://nextstrain.org/avian-flu/h5n1/ha/2y?c=host…. Sequence data is only available for HA, NA, MP, and NS, and the HA sequence is not complete. Still, a few observations:
1:22 PM · Sep 17, 2024
·
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Louise Moncla
@LouiseHMoncla
·
29m


Consistent with CDC reports, all available segments cluster within the cattle outbreak clade. The HA and NA sequences are placed on long branches, making it look like they are highly divergent. However, many of these "mutations" are simply gaps in the sequence.
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Louise Moncla
@LouiseHMoncla
·
24m


For example, if you shift-click on the tip, you can see that the HA sequence has 123 Ns. However, there are a few mutations of interest. Check out
@jbloom_lab
's excellent thread here for information on HA mutations of interest here:
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Bloom Lab
@jbloom_lab
·
Sep 15
Here is analysis of HA mutations in H5 influenza case in Missouri resident without known contact w animals or raw milk. TLDR: there is one HA mutation that strongly affects antigenicity, and another that merits some further study.


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Louise Moncla
@LouiseHMoncla
·
23m


If we visualize HA 172, we see that this mutation is generally quite rare, but is present in a cluster of cattle sequences and this human sequence. It is present in only 1 sampled bird sequence.
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Louise Moncla
@LouiseHMoncla
·
23m


This sequence is not currently available on the cattle build (https://nextstrain.org/avian-flu/h5n1-cattle-outbreak/genome?c=host&m=div…) because the sequence is incomplete. However, just placing it in the context of the trees above is enough to place it within the cattle cluster.


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Louise Moncla
@LouiseHMoncla
·
23m


Overall, this case is concerning primarily because it is unclear how this person was infected. Continued monitoring, rapid contact tracing, and expanded testing would be useful for determining how this happened.
 
Genotypic Clustering of H5N1 Avian Influenza Viruses Detected in North America

Tawidian, P.; Torchetti, M. K.; Killian, M. L.; Lantz, K.; Dilione, K. E.; Ringenberg, J. M.; Bevins, S. N.; Lenoch, J. B.; Ip, H. S. Genotypic Clustering of H5N1 Avian Influenza Viruses Detected in North America. Preprints 2024, 2024102401. https://doi.org/10.20944/preprints202410.2401.v1​

Version 1 : Received: 29 October 2024 / Approved: 30 October 2024 / Online: 31 October 2024 (03:42:04 CET)

Abstract

The introduction of HPAI H5N1 clade 2.3.4.4b viruses to North America in late 2021 resulted in avian influenza outbreaks in poultry, mortality events in many wild bird species, and spillover into many mammalian species. Reassortment events with North American low pathogenic virus were identified as early as February 2022 and over 100 genotypes have been characterized. Such diversity increases the complexity and time required for monitoring virus evolution. Here, we performed ordination and clustering analyses on sequence data from H5N1 viruses identified in North America between January 2020 to December 2023 to visualize virus genotypic diversity in poultry and wildlife populations. Our results reveal that ordination and cluster-based approaches can complement traditional phylogenetic analyses specifically for the preliminary assignment of H5N1 viruses to genotypic groups or to identify novel genotypes. Our study expands current knowledge on genotype diversity of H5N1 viruses in North America and describes a rapid approach for early virus genotype assignment.

​
​https://www.preprints.org/manuscript/202410.2401/v1
 
The human cases from poultry are D1.1 subclade and B3.13 subclade.

The human cases from cattle are B3.13 subclade.
 
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My bolding...




Raj Rajnarayanan
@RajlabN
·
4h


#H5N1 #AvianInfluenza Updates Quick analysis of the newly uploaded H5N1 sequences from human cases in #Washington These sequences contain NA S247N -- implicated in #antiviral drug resistance/reduced drug sensitivity 1/n
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Raj Rajnarayanan
@RajlabN
·
4h


Other NA mutations: V20I, M23V, Y44N, Q45H, P48T, I53V, V67I, F74L, L75I, T81D, S82P, T84A, I94T, V234I, V241I, S247N, K257R, D259E, G286S, D287E, I288V, N329S, S336G, M338V, E395A Reference: A/AmericanWigeon/SouthCarolina/22-000345-001/2021(H5N1) 2/n


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Raj Rajnarayanan
@RajlabN
·
3h


NA S247N - described in literature: less than 10 fold reduction in #Oseltamivir ad #Zanamivir sensitivity but no significant reduction in #Peramivir sensitivity. NA S247R is described to have a stronger impact 3/n


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Raj Rajnarayanan
@RajlabN


Link to literature source: "Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation" https://pubmed.ncbi.nlm.nih.gov/21679678/ 4/n

Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with...
From pubmed.ncbi.nlm.nih.gov
11:50 AM · Nov 14, 2024
·
1,095
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GISAID - British Columbia H5N1 Human Case Sequences uploaded - E627X indicated

H5N1 Bird Flu Circulating in Dairy Cows and Poultry in the United States

snip

Over a thousand full virus genome sequences from this outbreak, collected from mammalian and avian specimens in at least 18 States are shared via GISAID EpiFlu. Since the last update on 14. November, specimen data of British Columbia's first human case, a teenager who is currently hospitalized, with an unknown route of exposure (EPI_ISL_19548836) has been made available by British Columbia Centre for Disease Control (BCCDC). Additionally, specimen data from poultry, collected between 20. and 23. October, was made available by the Canadian Food Inspection Agency. The latest trees, based on representative subsamples, are dated to 15 November 2024.

​
H5N1 PB2 subsampled tree US 2024-11-15 at link


https://gisaid.org/resources/gisaid...nfluenza-outbreak-in-the-united-states/#c5130
 
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