Interestingly, the 1918, 1957 and 1968 pandemic viruses all had an avian-origin PB1 that enabled efficient replication at febrile temperatures.

I think this is one reason these pandemics caused so much severe disease.

We genetically isolated temperature sensitive replication by making point mutants in PB1. This allowed us to test 2 nearly identical viruses (one temp sensitive and the other temp resistant) in mice with a simulated fever (note that the mock traces are duplicated for clarity).

It is known that avian influenza A viruses replicate more effectively at fever-range temperatures than mammalian-adapted viruses. We found that avian-origin PB1 proteins predominantly confer fever-resistant replication.

Firstly thanks to all the authors who contributed to this project. A special shout out to Matt Turnbull who led this study and Yingxue Wang who took it over in Cambridge).

(Origami from Zhuonan Li)

Hi Bluesky! I’m a molecular virologist studying how innate immune defences restrict cross-species transmission and shape disease severity.

I just joined, so reposts appreciated to help me reconnect with virology, immunology, and host–pathogen interaction folks.

(whiteboard art from Zhuonan Li)