A new Science study examines why some avian-origin influenza A viruses continue to replicate in mammals even when fever develops. The findings highlight temperature-tolerance mechanisms that may be relevant for diagnostic interpretation, surveillance, and risk assessment of avian influenza spillover events.
Influenza A viruses are adapted to the body temperatures of their hosts. The study’s comparative schematic shows avian viruses replicate in the gastrointestinal tract of birds at about 40°C to 42°C. In contrast, human seasonal strains grow best in the cooler upper respiratory tract (around 33°C) and show reduced replication at higher temperatures. This difference is partly driven by the viral polymerase complex – especially the PB1 subunit.
The researchers engineered closely matched viruses that differed only in PB1 origin. They found that avian PB1 proteins enabled efficient replication at elevated temperatures in vitro, including PB1 variants present in the 1918, 1957, and 1968 pandemic viruses. By creating chimeric PB1 constructs, the team identified two amino acids responsible for this temperature resistance.
In mouse experiments, the parental laboratory PR8 strain showed poor replication at 40°C. Mice infected with PR8 under normal housing conditions developed severe disease, but when ambient temperature was increased to simulate fever, the same virus caused only mild illness. A PB1-modified “avianized” version of PR8, however, continued to replicate well at higher temperatures and caused severe disease even in febrile mice.
These results suggest that fever itself can restrict replication of temperature-sensitive influenza A viruses, but strains carrying avian-origin PB1 subunits may bypass this defense.
This study reinforces the value of genomic segment analysis – particularly PB1 origin – when evaluating influenza A viruses with unusual replication profiles or pathogenicity. Temperature tolerance linked to PB1 may help explain why some avian-derived or reassortant strains behave differently in culture or cause more-severe disease in humans.
The authors note that while febrile temperature is a meaningful antiviral barrier, it may not apply to all strains. Incorporating polymerase gene characteristics into routine molecular assessments could improve early risk evaluation of avian-origin viruses detected in clinical or environmental samples.
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