An emerging PB2-627 polymorphism increases the zoonotic risk of avian influenza virus by overcoming ANP32 host restriction in mammalian and avian hosts
Bibliographic record
Abstract
Alterations in the PB2-627 domain of avian influenza virus (AIV) can potentially increase the risk of cross-host species infections in humans and mammals. Recently, there has been a rise in human cases of AIV infections without the presence of the known mammalian determinant PB2-E627K. Here, we identified a variant, PB2-627V, which has evolved in poultry and has contributed to the increase in human AIV infections. By screening global PB2 sequences, we discovered a new independent cluster of PB2-627V that emerged in the 2010s, prevalent in avian, mammalian, and human AIV isolates, including those of H9N2, H7N9, H3N8, 2.3.4.4b H5N1, and other subtypes. We functionally assessed its host adaptation, fitness, and transmissibility across three subtypes of AIVs (H9N2, H7N9, and H3N8) in different host models. PB2-627V combines the viral properties of avian-like PB2-627E and human-like PB2-627K, facilitating AIVs to efficiently infect and replicate in chickens and mice by utilizing both avian- and human-origin ANP32A proteins. Importantly, PB2-627V promotes efficient transmission between ferrets through respiratory droplets. Deep sequencing of passaged chicken and transmitted ferret viral samples indicates that PB2-627V remains stable across the two host species and shows a high potential for long-term prevalence in avian species. Thus, the PB2-627V mutation in AIVs can stably transmit through poultry and can overcome the cross-species barrier to infect humans. Given the global prominence of AIVs, it will be prudent to monitor influenza viruses for the PB2-627V mutation as a potential marker for zoonotic spread.IMPORTANCEAvian influenza viruses (AIVs) are significant zoonotic pathogens. There is a rising trend of human cases of AIVs caused by a range of virus subtypes, including H9N2, H3N8, and H5N1 viruses. Thus, it is crucial to understand the underlying viral changes in AIVs that could result in zoonotic spread. We identify mutation PB2-627V as an emerging viral factor that confers dual ability to the virus to infect and adapt to mammalian and avian hosts, and virus transmissibility in ferrets. The presence of PB2-627V in multiple subtypes of AIVs has the potential to cause public health risk. We therefore propose that PB2-627V be included as a molecular marker to assess the zoonotic risk of AIVs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".