Poster Presentation 12th Australasian Virology Society Meeting 2024

Replication of contemporary A(H1N1)pdm09, A(H3N2) and B Victoria lineage influenza viruses in the upper and lower respiratory tract of ferrets. (#168)

Harry Stannard 1 , Paulina Koszalka 1 , Smitha Georgy 2 , Nikita Deshpande 1 , Kanta Subbarao 1 3 , Saira Hussain 1 , Ian Barr 1 , Patrick Reading 1 3
  1. WHO Collaborating Centre for Reference and Research on Influenza, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  2. Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Melbourne, VIC, Australia
  3. Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia

Introduction:

Ferrets are widely considered to be the gold-standard small animal model to study the pathogenesis of influenza viruses, as well as the impact of vaccines and antiviral drugs on influenza infections. The seasonal human influenza viruses, A(H1N1)pdm09, A(H3N2) and B/Victoria (B/Vic) lineage viruses all replicate efficiently in the upper respiratory tract (URT) of ferrets. While all can cause lower respiratory tract (LRT) disease in humans, only A(H1N1)pdm09 viruses demonstrate efficient replication in the LRT of ferrets. This study aimed to compare the ability of different A(H1N1)pdm09, A(H3N2) and B/Vic viruses to replicate in both the URT and LRT of ferrets.

Methods:

Ferrets were inoculated via the intranasal route with influenza cell-grown virus isolates from 1997-2022. At 3- or 5-days post-infection, URT (nasal tissues) and LRT (individual lung lobes) samples were collected to determine viral titres and/or histopathological analysis.

Results:

All viruses tested replicated efficiently in the URT of ferrets however marked differences were noted in virus titres recovered from the LRT. All five A(H1N1)pdm09 viruses tested replicated in the LRT, allowing us to identify a recent (A/Sydney/5/2021) virus that replicated most efficiently in the LRT and showed enhanced lung pathology scores compared to the earlier viruses. Following infection with 18 A(H3N2) and 8 B/Vic viruses, we identified only a few viruses with detectable viral loads in one or more ferret lung lobes.

Conclusions:

Compared to A(H1N1)pdm09 viruses from 2009-2019, we identified a recent (A/Sydney/5/2021) virus which showed enhanced lung virus titres and histopathology. Ongoing studies aim to characterise the A(H3N2) and/or B/Vic strains that replicated in the LRT of ferrets and to identify factors that limit the growth of most A(H3N2) and B/Vic viruses tested. Together, these studies aim to improve experimental models to examine the efficacy and the breadth of current and novel anti-influenza treatments in ferrets.