A future natural influenza pandemic is inevitable, and the risk appears to be very high at the current timebecause of the widespread avian influenza outbreak with direct infections of humans occurring in countries inSoutheast Asia and the Middle East since 2004, with >58% mortality for the documented human cases. TheH5N1 avian virus has spread throughout Asia in poultry populations. There is increasing concern that thewidespread outbreak of avian H5N1 in Asia will lead to co-infection of humans concurrently infected withhuman H1N1 and H3N2 strains, resulting in reassortant virus strains that can accomplish human-to-humanspread and initiate the next influenza pandemic, with increased mortality (even if not fully 58%) for thoseinfected.Information regarding the potential avian-human reassortant combinations would be key to establishingpandemic preparedness, including assessment of susceptibility of the likely strains to licensed ordevelopmental antiviral agents, and identification of the most important reassortant strains for targetedvaccine development.The hypothesis to be tested is whether human (H1N1 or H3N2) and avian H5N1 influenza virus genesare compatible and have the potential to generate a pandemic influenza virus. The available informationwould suggest that this should be very likely but we do not know if it is possible since not all influenza genecombinations are necessarily compatible.
The Specific Aims of this project are: (1) To determine thepotential for reassortment to occur between current human (H1N1 or H3N2) influenza viruses and an avianH5N1 influenza virus from a human case of infection in Vietnam and/or Indonesia; (2) To determine if theresultant reassortant viruses are pathogenic in embryonated chicken eggs and mammalian cells, includinghuman leukocytes; (3) To determine if the resultant reassortant viruses are infectious for mice withoutadaptation and to determine whether they are highly pathogenic for the mice; (4) To determine if theresultant reassortant viruses are susceptible to current antiviral agents, such as the licensed neuraminidaseinhibitors, or agents in development.This project represents a collaborative project between investigators at UTMB and St. Jude Children'sResearch Hospital as outlined in the original application. With the move of the St. Jude PI to UTMB, no directcosts will ensue in the coming project period for St. Jude (and thus there is no need or request for acontinued subcontract). However, the outcome of these studies (publications and/or products developed) willbe viewed as (and will reflect) a continued collaboration of Dr. Roberts and his colleagues with Dr. R.G.Webster at St. Jude.
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