LB-22. In Vivo Evaluation of the Pathogenicity and Transmissibility of pH1N1 Hemagglutinin Receptor 222 Variants Isolated from a Severely Ill Immunocompromised Patient
Session: Poster Abstract Session: Late Breaker Posters
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • IDSA Poster 2011 LB-22.png (432.7 kB)
  • Background: 

    The 2009 pandemic H1N1 virus has circulated worldwide for two influenza seasons and continued to cause complicated infections and deaths.  Reports have identified an increased prevalence of the HA receptor domain D222G mutation in viruses isolated from individuals who have suffered such severe infections, but the relationship of this mutation to severe disease is still unclear.  We isolated viruses from an immunocompromised patient who developed a complicated influenza infection.  Virus isolated from a nasal wash at the time of diagnosis contained the consensus D222 at this amino acid position, but isolates later in his course collected from a BAL contained primarily the G222 mutation while those from nasal wash samples continued to contain the D222.  Further analysis demonstrated that the BAL sample contained a mixed population containing a majority G222 and minor population of D222.   The significance of this was evaluated in the ferret model.

    Method:

    Plaque purification was performed on the D222/G222 mixed BAL isolate to purify a population of virus with G222.  This virus was administered to a group of ferrets, as were the original mixed BAL isolate, and the original D222 containing viral isolated from this patient.  Clinical disease, shedding, transmission, pathology, and post infection viral isolate analysis was performed.

    Result: 

    The plaque purified virus containing G222 caused the least disease and pathology in the animals, despite being able to transmit efficiently and grow in both the upper and lower airways.  The mixed D222/G222 BAL isolate caused the most significant and severe disease in ferrets including death, especially in those animals who acquired the virus by contact.  Although the nasal wash isolate containing the D222 caused noticeable disease, it was not as severe as that of the mixed isolate and grew to a lower titer in the lungs of animals after contact transmission.

    Conclusion: 

    In the ferret model, the HA D222G mutation does not mediate severe disease alone, but as a dominant component of a mixed viral population it may play a role in enhancing pathogenesis.  These results suggest that the genetic diversity of a viral inoculum may be clinically import and play a significant role in disease progression and outcome in influenza infection.


    Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

    Matthew J. Memoli, MD, MS, Kathleen Proudfoot, Tyler Bristol, A. Sally Davis, DVM and Jeffery Taubenberger, MD, PhD, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

    Disclosures:

    M. J. Memoli, None

    K. Proudfoot, None

    T. Bristol, None

    A. S. Davis, None

    J. Taubenberger, None

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