Rare recovery of reassortants between contemporary clade 2.3.4.4b H5N1 viruses and human influenza A viruses in vitro.

Contemporary clade 2.3.4.4b H5N1 influenza A viruses generated viable reassortants with human H1N1/H3N2 IAVs at a 0.74% recovery rate in vitro.

• Why it matters: Pandemic risk depends on whether animal and human influenza viruses can exchange genome segments, yet it was unclear if contemporary H5N1 can form viable reassortants with human strains.
• What they did: Using a biosafe reassortment system, two clade 2.3.4.4b H5N1 viruses were co-infected with human-adapted H1N1 and H3N2 IAVs, and 2,698 plaque-purified clones were genotyped. Polymerase assays then tested which human subunits affected H5N1 polymerase activity.
• The result: Twenty reassortants were recovered (0.74%), and human IAV subunits—especially H1N1 PA or H3N2 PB2—were linked to increased H5N1 polymerase activity, implying other constraints may limit recovery.

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