BREAKING! Study Finds That New H5N1 Strain: Subtype Clade 2.3.4.4b With The Mutation PB2 T271A Has Capacity For Airborne Transmissions!

H5N1 News: In a significant development, researchers have discovered that a strain of the H5N1 influenza virus has acquired the ability for airborne transmission. This revelation, emerging from a study that is covered in this H5N1 News report, highlights the evolving threat of H5N1 viruses to mammals, including humans. This study marks the first instance of an H5N1 subtype clade 2.3.4.4b virus demonstrating such airborne transmissibility.


Airborne transmission, weight loss and survival for ferrets infected with PB2 A271T A/mink (H5N1).
Four donor ferrets were inoculated with A/mink (H5N1) PB2 A271T and 24 h later each donor was paired with a single respiratory contact in a transmission cage. Nasal wash samples were collected every other day for 14 days, and weight loss and clinical signs were monitored. A, C, and B, D display viral titers and weight loss from individual donor and respiratory contacts, respectively. DR and RC denote donor and respiratory contact, respectively. Each bar or line represents an individual animal. Males are DR1, DR2, RC1 and RC2 and females are DR3, DR4, RC3 and RC4. E denotes euthanasia. Ferret DR4 was euthanized on day 10 due to pronounced weight loss. Dotted line denotes limit of detection.

The research, led by scientists at Penn State University, focused on the PB2 T271A mutation found in a strain previously linked to an outbreak among farmed mink in Spain. The study’s findings underscore the need for vigilant monitoring of these viruses, given their potential to spill over into humans.
 
First Detection in Dairy Cattle
In a surprising turn of events, the United States reported its first case of highly pathogenic H5N1 avian influenza in dairy cattle in March. By May, the virus had spread across nine states. The exact mode of transmission among cattle remains uncertain, adding another layer of complexity to the ongoing investigation. The Penn State study, however, provides crucial insights into the airborne transmission capabilities of a similar H5N1 strain, raising alarms about its pandemic potential.
 
Understanding Airborne Transmission
To evaluate the airborne transmission potential of the H5N1 virus, the research team reconstructed the virus using genetic sequences available from public databases. They then conducted experiments using ferrets, which share similar respiratory tract characteristics with humans, making them an ideal model for studying influenza virus transmission.
 
The team assessed both direct and indirect transmission by placing infected ferrets in close proximity to uninfected ones. The results were alarming: 75% of ferrets exposed to the virus through direct contact became infected, while 37.5% of those exposed to airborne particles also contracted the virus. This demonstrated that even a small amount of the virus could cause infection, highlighting its low infectious do se.

The Role of Mutation PB2 T271A
A critical aspect of this study was understanding the role of the PB2 T271A mutation in the virus’s ability to transmit and cause disease. The researchers engineered a version of the virus without this mutation and observed a significant reduction in both mortality and airborne transmission among the ferrets.

“These findings suggest that the PB2 T271A mutation enhances viral replication, contributing to both virulence and transmission,” said Dr Troy Sutton, the study’s corresponding author. This discovery is pivotal as it allows for targeted surveillance of similar mutations in circulating H5N1 strains, providing an early warning system for potential outbreaks.
 
Implications for Human Health
While the study offers crucial insights, it also emphasizes that the ferrets used had no preexisting immunity to influenza, unlike the majority of humans who have been exposed to H1N1 and H3N2 seasonal influenza viruses. This prior exposure could offer some level of cross-protection against H5N1, potentially mitigating the impact of the virus on humans.
 
However, Dr Sutton noted that the transmission rate observed in the mink strain is lower than that typically seen in pandemic influenza viruses. “Pandemic influenza viruses usually transmit via the airborne route to 75% to 100% of contacts within three to five days, whereas the mink virus transmitted to fewer than 40% of contacts after nine days,” he explained.
 
This lower transmission rate does not eliminate the risk but suggests that while the virus has pandemic potential, it does not yet possess the same attributes as known pandemic strains. The strain affecting cattle has not caused severe disease in cattle or humans so far. However, the longer the virus circulates and the more humans are exposed to it, the higher the chances of it evolving to become more infectious to humans.
 
Global Perspective and Historical Context
The H5N1 viruses, originating from the A/goose/Guangdong/1/1996 lineage, have long posed a pandemic threat. Since their emergence in Asia, nearly 900 human cases have been reported worldwide, with a staggering 50% mortality rate. The new H5N1 variant, belonging to subclade 2.3.4.4b, has rapidly spread across continents, causing ecological devastation and large die-offs among wild bird populations.
 
In late 2021, this subclade was first detected in North America and has since spread to South America, affecting both wild and domestic bird populations. The virus has spilled over into several mammalian species, including skunks, foxes, bears, and seals. Seven human infections with subclade 2.3.4.4b H5N1 viruses have been documented between January 2022 and March 2023.
 
Experimental Insights and Broader Implications
The researchers' experimental approach, involving ferrets, revealed that the H5N1 virus could transmit efficiently through direct contact and less efficiently through airborne routes. Sequence analyses indicated that transmission was not linked to specific mutations, suggesting that the virus’s ability to infect and spread among mammals could be due to other factors.
 
In dose de-escalation studies, the A/mink (H5N1) virus showed a low infectious dose and high virulence across various doses, causing severe disease in all infected animals. This virulence was observed even at minimal doses, underscoring the virus’s potential danger.
 
Moreover, the PB2 T271A mutation played a significant role in enhancing the virus's replication and transmission. When this mutation was reversed, the virus showed reduced polymerase activity, decreased mortality, and diminished airborne transmission. These findings highlight the critical impact of specific genetic mutations on the virus's behavior and potential to cause pandemics.
 
Future Directions and Surveillance
Given the findings, ongoing risk assessment and enhanced surveillance in wild and domestic animals are crucial. The study emphasizes the importance of monitoring viral evolution and the emergence of new mutations that could increase the virus’s transmissibility and virulence.
 
The researchers also pointed out that ferrets used in the study lacked pre-existing immunity to influenza, which is not the case for most humans. Future studies should explore how prior exposure to seasonal influenza strains might affect disease severity and transmission of H5N1.

In conclusion, this groundbreaking study sheds light on the evolving threat of H5N1 influenza viruses, particularly the impact of the PB2 T271A mutation on airborne transmission. The findings underscore the urgent need for continuous surveillance and preparedness to mitigate the potential pandemic threat posed by these viruses as they continue to evolve and spread.
 
The study findings were published in the peer reviewed journal: Nature Communications.
https://www.nature.com/articles/s41467-024-48475-y
 
For the latest H5N1 News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/breaking-h5n1-genotype-affecting-cows-in-america-possibly-gains-entry-into-humans-via-the-eyes-thru-the-new-pb2-e67k-mutation
 
Check Out:
https://www.thailandmedical.news/articles/h5n1-avian-flu