TY - JOUR
T1 - The immune response and within-host emergence of pandemic influenza virus
AU - Reperant, Leslie A.
AU - Kuiken, Thijs
AU - Grenfell, Bryan T.
AU - Osterhaus, Albert D.M.E.
N1 - Funding Information:
We thank Guus Rimmelzwaan (Department of Viroscience, Erasmus Medical Centre, Netherlands), and Derek Smith and Judy Fonville (Department of Zoology, University of Cambridge, UK) for productive discussions. LAR was supported by EU FP7 Marie-Curie International Incoming Fellowship #302060; TK by EU FP7 ANTIGONE project #278976; BTG by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, NIH, Department of Homeland Security contract HSHQDC-12-C-00058, and the Bill & Melinda Gates Foundation; and ADMEO by EU FP7 EMPERIE project #223498 and EU FP7 ANTIGONE project #278976. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/12/6
Y1 - 2014/12/6
N2 - 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.
AB - 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.
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U2 - 10.1016/S0140-6736(13)62425-3
DO - 10.1016/S0140-6736(13)62425-3
M3 - Comment/debate
C2 - 24767965
AN - SCOPUS:84919871397
SN - 0140-6736
VL - 384
SP - 2077
EP - 2081
JO - The Lancet
JF - The Lancet
IS - 9959
ER -