The immune response and within-host emergence of pandemic influenza virus.
Zoonotic influenza viruses that are a few mutations away from pandemic viruses circulate in animals, and can evolve into airborne-transmissible viruses in human beings. Paradoxically, such viruses only occasionally emerge in people; the four influenza pandemics that occurred in the past 100 years were caused by zoonotic viruses that acquired efficient transmissibility. Emergence of a pandemic virus in people can happen when transmissible viruses evolve in individuals with zoonotic influenza and replicate to titres allowing transmission. We postulate that this step in the genesis of a pandemic virus only occasionally occurs in human beings, because the immune response triggered by zoonotic influenza virus also controls transmissible mutants that emerge during infection. Therefore, an impaired immune response might be needed for within-host emergence of a pandemic virus and replication to titres allowing transmission. Immunocompromised individuals--eg, those with comorbidities, of advanced age, or receiving immunosuppressive treatment--could be at increased risk of generating transmissible viruses and initiating chains of human-to-human infection.
Department of Viroscience, Erasmus Medical Centre, Rotterdam, Netherlands; Artemis Research Institute for One Health in Europe, Utrecht, Netherlands. Electronic address: l.reperant@erasmusmc.nl.
Leslie A
LA
Reperant
Department of Viroscience, Erasmus Medical Centre, Rotterdam, Netherlands.
Thijs
T
Kuiken
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
Bryan T
BT
Grenfell
Department of Viroscience, Erasmus Medical Centre, Rotterdam, Netherlands; Artemis Research Institute for One Health in Europe, Utrecht, Netherlands.
Albert D M E
AD
Osterhaus
D000818:Animals; D006801:Humans; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology / Q000635:transmission; D008962:Models, Theoretical; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000453:epidemiology* / Q000276:immunology / Q000635:transmission; D058873:Pandemics; D011634:Public Health; D015047:Zoonoses / Q000635:transmission