Flu Virus binding to Receptor Cells – Credit CDC
#18,963
- In November of 2024, we learned of a severe case involving a teenage girl in British Columbia (see NEJM: Critical Illness in an Adolescent with Influenza A(H5N1) Virus Infection)
- The following January the Louisiana Department of Health Announced the 1st U.S. H5N1-related Fatality
- And a Fatal case was reported in Mexico (see WHO DON Update On Mexico's Fatal H5N1 Infection) in April.
A total of 53 strains were identified, of which 6 strains had 2 sequences deposited. These 53 strains were collected from patients between March 28, 2024 and February 12, 2025 (Supplementary Table S3). Of these 53 strains, 22 (41.5%) were assigned to genotype B3.13, 8 (15.1%) were assigned to D1.1, 1 (1.9%) was assigned to D1.3, and 22 (41.5%) could not be assigned to any genotypes according to GenoFLU version 1.06 (https://github.com/USDA-VS/GenoFLU).
It appears, however, that Bovine B3.13 human infections have likely outnumbered D1.1 infections by a factor of 2:1, making the difference in virulence even more pronounced.
Today's report, from researchers at the University of Hong Kong, provides some insight on why D1.1 human infections appear to be more severe than B3.13.
They demonstrate that the D1.1 genotype replicates better in lab-grown nasal and lung tissues than the bovine B3.13 strain, and it binds more tightly to human‑type (α2,6-linked SA) receptors.
I've reproduced the abstract, and a brief excerpt, below. Follow the link to read the full report. I'll have a bit more after the break.
Xiaojuan Zhang, Stephanie Joy-Ann Lam, Lin-Lei Chen, Carol Ho-Yan Fong, Wan-Mui Chan, Jonathan Daniel Ip, Shaofeng Deng, Siwen Liu, Rachel Chun-Yee Tam, Pui Wang
The Journal of Infectious Diseases, jiaf598, https://doi.org/10.1093/infdis/jiaf598
Published:24 November 2025 Article history
Abstract
Three critically ill or fatal avian influenza A(H5N1) human infections have been reported in North America since November 2024. Notably, all were infected with genotype D1.1 instead of B3.13, the dominant genotype before November 2024. Here, we demonstrated that D1.1 could replicate to higher titers in human nasal and airway organoid-derived transwell monolayers from 6 donors.
D1.1 exhibited a better binding to α2,3- and α2,6-linked SA than B3.13. No significant differences in most inflammatory or antiviral cytokines/chemokines was observed. These observations suggest that D1.1 is better adapted to both the upper and lower human respiratory tract epithelium than B3.13.
(SNIP)
Our observations suggest that D1.1 genotype may be better adapted to humans than B3.13. Further studies are required to determine if there are differences in the replication of different strains within the same clade. As D1.1 is now widespread among dairy cows in the United States, there is an increasing risk of further adaptation of D1.1 with higher transmissibility or virulence among mammals. Continuous phenotypic monitoring using human organoids and other in vivo models will provide critical information for assessing the risk of D1.1 or other novel genotypes in humans.
Almost 13 years ago, in Differences In Virulence Between Closely Related H5N1 Strains, we looked at the varying impact of HPAI H5N1 viruses around the globe. Some countries saw CFRs (Case Fatality Rates) of 50%-80%, while others reported relatively few deaths (see chart below).
While we're thankfully not seeing the kind of high CFR H5N1 in North America and Europe that once was far too common in Indonesia, Vietnam, and Egypt, the events over the past 3 years in Cambodia remind us that severe H5N1 still exists.
And recent offshoots of H5N1 - like the H5N5 case in Washington State and the Novel Reassortant H5N2 case in Mexico - demonstrate that these HPAI viruses continue to reinvent themselves at a rapid pace.
Whether this ultimately leads to another pandemic is anyone's guess, but right now HPAI H5 appears to be on a roll, and should give all of us pause.
