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Assessing Mathematical Models of Influenza Infections Using Features of the Immune Response

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journal contribution
posted on 2021-05-21, 11:59 authored by Hana M. Dobrovolny, Micaela B. Reddy, Mohamed A. Kamal, Craig R. Rayner, Catherine A. A. Beauchemin

The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. Inorder to identify severity factors and more accurately predict the course of an influenza infection within a human host, anunderstanding  of  the  impact  of  host  factors  on  the  infection  process  is  required.  Despite  the  lack  of  sufficiently  diverseexperimental  data  describing  the  time  course  of  the  various  immune  response  components,  published  mathematical models  were  constructed  from  limited  human  or  animal  data  using  various  strategies  and  simplifying  assumptions.  Toassess  the  validity  of  these  models,  we  assemble  previously  published  experimental  data  of  the  dynamics  and  role  ofcytotoxic  T  lymphocytes,  antibodies,  and  interferon  and  determined  qualitative  key  features  of  their  effect  that  should  becaptured by mathematical models. We test these existing models by confronting them with experimental data and find thatno  single  model  agrees  completely  with  the  variety  of  influenza  viral  kinetics  responses  observed  experimentally  whenvarious  immune  response  components  are  suppressed.  Our  analysis  highlights  the  strong  and  weak  points  of  eachmathematical   model   and   highlights   areas   where   additional   experimental   data   could   elucidate   specific   mechanisms,constrain  model  design,  and  complete  our  understanding  of  the  immune  response  to  influenza.