Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model.
BACKGROUND
Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference.


METHODS
Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010.


RESULTS
Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge.


CONCLUSIONS
The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity School of Applied and Biomedical Sciences, Federation University, Churchill, Australia.
Karen L
KL
Laurie
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity School of Applied and Biomedical Sciences, Federation University, Churchill, Australia.
Teagan A
TA
Guarnaccia
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity.
Louise A
LA
Carolan
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne.
Ada W C
AW
Yan
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity.
Malet
M
Aban
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne.
Stephen
S
Petrie
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne.
Pengxing
P
Cao
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne Modelling Infection and Immunity Laboratory, Centre for Disease Modelling, York Institute for Health Research Program in Mathematics and Statistics, York University, Toronto, Canada.
Jane M
JM
Heffernan
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne Modelling and Simulation Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne.
Jodie
J
McVernon
School of Applied and Biomedical Sciences, Federation University, Churchill, Australia.
Jennifer
J
Mosse
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity.
Anne
A
Kelso
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne Modelling and Simulation Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne.
James M
JM
McCaw
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity School of Applied and Biomedical Sciences, Federation University, Churchill, Australia.
Ian G
IG
Barr
D000818:Animals; D060085:Coinfection; D004195:Disease Models, Animal; D005289:Ferrets; D006801:Humans; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology*; D009975:Orthomyxoviridae / Q000276:immunology*; D014762:Viral Interference / Q000276:immunology*; D017201:Virus Shedding
A(H1N1)pdm09; A(H3N2); ferret; hierarchy; influenza; influenza B; pandemic; seasonal influenza; temporary immunity; viral interference