Replication of seasonal H1N1 influenza virus after inhalation less efficient than H3N2 virus

According to a new study published in PLOS ONE, the seasonal H1N1 virus may replicate less efficiently than H3N2 virus after mucosal deposition and exhibit less contagion after aerosol exposure.

Influenza virus is a common cause of serious respiratory infection, pneumonia and mortality worldwide every year and periodically new strains of influenza virus cause worldwide pandemics.  Worldwide and local circulation of any influenza virus depends in part on previous exposure to similar cross-reacting viruses and in part on the inherent transmissibility of the virus. 

Person-to-person transmission can occur by direct contact or through the air by infectious aerosol.  Surprisingly little quantitative understanding of transmission is available to design strategies to reduce transmission. 

Image credit: Dr. Frederick Koster

Ferrets and guinea pigs are excellent animal models of influenza transmission and have provided insights into the relative transmission efficiencies of pandemic and seasonal strains.  Nonetheless the minimal infecting dose by the aerosol or contact route has rarely been measured.

Ferrets were exposed to a aerosolized seasonal H1N1 influenza virus strain, closely related to H1N1 viruses circulating worldwide in the 1990’s, in a chamber with controlled airflow.  The ferrets inhaled 10% of the viral aerosol, containing airborne particles less than 5 microns in diameter, the size that can remain suspended in the air for hours.   During exposures the airborne virus was sampled by two methods, liquid impingers able to collect live virus but less quantitative, and Teflon filters unable to capture live virus but able to collect total airborne viral genomic RNA measured with a high-throughput RT-PCR/mass spectrometry assay developed by Ibis Biosciences Inc. (T5000TM Biosensor system).    Since very low levels of virus were expected to cause infection, the precision of minimal dose estimation was calculated from both the ratio of live virus-to-viral RNA in impingers and the  total Teflon filter-collected viral RNA.

The minimal infectious dose of aerosolized H1N1 virus was approximately 4 infectious virus particles under the exposure conditions used.   Although seroconversion and sustained levels of viral RNA in upper airway secretions indicated established mucosal infection, the ferrets did not develop symptoms. In related work submitted for publication, aerosol transmission from infected ferret to susceptible ferret using the same chamber design resulted in no transmission of the seasonal strain but robust transmission of the pandemic 2009 H1N1 virus.  Thus viral replication of this seasonal H1N1 virus after inhalation was less efficient than a more robust seasonal H3N2 virus in studies published by the Centers for Disease Control.  Future experiments need to test the implication that, in contrast to direct contact exposure, infection after aerosol exposure to some influenza strains is not associated with either symptoms or contagion to other individuals.  

Reference Publication: MacInnes H, Zhou Y, Gouveia K, Cromwell J, Lowery K, et al. (2011) Transmission of Aerosolized Seasonal H1N1 Influenza A to Ferrets. PLoS ONE 6(9): e24448. doi:10.1371/journal.pone.0024448