Progress 09/15/07 to 09/14/12
Outputs
Progress Report Objectives (from AD-416): 1) Pathogenesis of avian inluenza virus isolates in swine; 2) Role of avian polymerases in adaptation of swine influenza viruses to swine; 3) Genetic characterization of swine and avian influenza viruses to swine; and 4) Preparation of reagents. Approach (from AD-416): 1) Pathogenesis of avian influenza virus isolates in swine will be evaluated after inoculation into a group of four week old pigs. Microscopic and macroscopic lung lesions and viral replication in lungs and nasal cavities will be determined. 2) Various reassortant viruses containing avian and/or swine polymerase genes will be established using reverse genetics approaches. These reassortant viruses will be tested for their pathogenic potential in swine. 3) Swine and avian influenza isolates will be genetically characterized using conventional sequencing approaches. 4) Hyperimmune sera and various viruses will be made available as reagents. In the 1980s swine were proposed to be the "mixing vessel" for novel influenza viruses that could infect humans. This hypothesis was based on the identification of human-like and avian-like influenza virus receptors in the respiratory tract of swine. The presence of both receptors could allow pigs to be simultaneously infected with a human and avian influenza virus leading to the formation of a new virus that reflected the combination of the avian and human viruses. This novel virus would be transmitted to people and could lead to a pandemic. In the late 1990s an H5N1 influenza virus emerged in birds that sporadically jumped species to people often resulting in severe disease and death. The lethality of this virus for humans was of great concern and led to the formation of a long- term multi-institutional NIH-funded grant to study various aspects of the ecology and biology of influenza viruses. The National Animal Disease Center's initial role in this grant was to study molecular mechanisms by which influenza viruses acquire increased disease causing capacity or pathogenicity for humans and animals, and determination of the molecular mechanisms responsible for the transmission of influenza viruses between animals, between humans, and from animals to humans. Animal models used to study the molecular pathogenesis of human influenza virus infections have revealed a number of putative mechanisms that relate to how the virus can infect humans and cause disease. Based on a mouse model, a specific sequence in the influenza virus PB2 gene contributes to its pathogenicity. This same effect was not detected in swine indicating the complexity of using animal models. These differences are attributed to differences among species, and to the fact that influenza virus-swine is a natural virus-host interaction compared to the adaptation of human influenza viruses to mice for experimental purposes. Following changes in personnel and funding, the objectives of the grant were modified to conduct animal inoculation studies testing the susceptibility of swine to infection with low pathogenic avian and human influenza A viruses. To test the first part of the mixing vessel hypothesis, swine studies were initiated to inoculate pigs with an avian influenza virus (low pathogenic H5 and H7 viruses, and H9 isolates) or with human H1N1 influenza viruses. Pigs were shown to be susceptible to single experimental infection with avian or human influenza A virus isolates. Depending on isolate, minimal to mild clinical disease was produced suggesting swine could act as a reservoir for various influenza viruses and might serve as a mixing vessel. Studies designed to evaluate dual infections with avian and human viruses were put on hold with the emergence of the 2009 H1N1 pandemic virus of swine origin that contained avian and human genes, the product of a perfect mixing vessel experiment that proved the hypothesis. As part of a nationwide response to the pandemic, swine studies were re-designed to investigate the pathogenesis of the pandemic virus. In addition, plans were made to conduct collaborative studies evaluating the consequences highly pathogenic avian influenza viruses infections in swine and the potential for formation of unique viruses. However, a change in regulations delayed this proposed work and will require modification of research plans to investigate interspecies transmission of a new group of swine influenza viruses. The new lineage of viruses is of concern based on the growing number of swine to human transmission events that have occurred during the last year. This summary report covers the first 5 years of the 7-year-long grant, and the research under the multi- institutional grant that continues into 2014 will be documented in a new ARS subordinate project number.
Impacts
(N/A)
Publications
|
Progress 10/01/10 to 09/30/11
Outputs
Progress Report Objectives (from AD-416) 1) Pathogenesis of avian inluenza virus isolates in swine; 2) Role of avian polymerases in adaptation of swine influenza viruses to swine; 3) Genetic characterization of swine and avian influenza viruses to swine; and 4) Preparation of reagents. Approach (from AD-416) 1) Pathogenesis of avian influenza virus isolates in swine will be evaluated after inoculation into a group of four week old pigs. Microscopic and macroscopic lung lesions and viral replication in lungs and nasal cavities will be determined. 2) Various reassortant viruses containing avian and/or swine polymerase genes will be established using reverse genetics approaches. These reassortant viruses will be tested for their pathogenic potential in swine. 3) Swine and avian influenza isolates will be genetically characterized using conventional sequencing approaches. 4) Hyperimmune sera and various viruses will be made available as reagents. This is the fifth year of a 7-year-project that is part of a multi- institutional grant. The National Animal Disease Center's role is to conduct studies testing the susceptibility of swine to infection with selected non-swine influenza viruses. Previously, pigs were shown to be susceptible to infection with H9, H7, and H5 influenza A subtype viruses. The studies demonstrated that pigs are susceptible to a number of isolates in these subtypes. As part of the response to the emergence of the pandemic 2009 H1N1 virus, the susceptibility of pigs to recent H1N1 seasonal human influenza viruses was tested. Similar to the avian studies, pigs could be infected with the viruses, but developed little if any clinical disease following infection. Collectively, the studies support the assumption that pigs can be infected with many different types of influenza. This observation supports the hypothesis that swine can serve as a potential mixing vessel for avian and human influenza viruses leading to the production of novel influenza viruses. Progress was monitored via email and conference calls.
Impacts
(N/A)
Publications
|
Progress 10/01/09 to 09/30/10
Outputs
Progress Report Objectives (from AD-416) 1) Pathogenesis of avian inluenza virus isolates in swine; 2) Role of avian polymerases in adaptation of swine influenza viruses to swine; 3) Genetic characterization of swine and avian influenza viruses to swine; and 4) Preparation of reagents. Approach (from AD-416) 1) Pathogenesis of avian influenza virus isolates in swine will be evaluated after inoculation into a group of four week old pigs. Microscopic and macroscopic lung lesions and viral replication in lungs and nasal cavities will be determined. 2) Various reassortant viruses containing avian and/or swine polymerase genes will be established using reverse genetics approaches. These reassortant viruses will be tested for their pathogenic potential in swine. 3) Swine and avian influenza isolates will be genetically characterized using conventional sequencing approaches. 4) Hyperimmune sera and various viruses will be made available as reagents. This is the fourth year of a 7-year-project that is part of a multi- institutional grant. The National Animal Disease Center's role is to conduct studies testing the susceptibility of swine to infection with low pathogenic avian influenza viruses. Pigs were shown to be susceptible to infection with H9 influenza A subtype viruses similar to when swine are inoculated with the H5 and H7 influenza subtype viruses. Although the pigs can become infected, there appears to be little shedding of the virus to contact pigs. Collectively, these studies support the assumption that pigs can be infected with many different types of influenza.
Impacts
(N/A)
Publications
|
Progress 10/01/08 to 09/30/09
Outputs
Progress Report Objectives (from AD-416) 1) Pathogenesis of avian inluenza virus isolates in swine; 2) Role of avian polymerases in adaptation of swine influenza viruses to swine; 3) Genetic characterization of swine and avian influenza viruses to swine; and 4) Preparation of reagents. Approach (from AD-416) 1) Pathogenesis of avian influenza virus isolates in swine will be evaluated after inoculation into a group of four week old pigs. Microscopic and macroscopic lung lesions and viral replication in lungs and nasal cavities will be determined. 2) Various reassortant viruses containing avian and/or swine polymerase genes will be established using reverse genetics approaches. These reassortant viruses will be tested for their pathogenic potential in swine. 3) Swine and avian influenza isolates will be genetically characterized using conventional sequencing approaches. 4) Hyperimmune sera and various viruses will be made available as reagents. Significant Activities that Support Special Target Populations This is the third year of a 7-year project that is part of a multi- institutional grant. With the departure of an ARS scientist to Kansas State University, the role of the National Animal Disease Center (NADC) in this grant has changed. The new objective is to conduct animal inoculation studies to test the susceptibility of swine to infection with low pathogenic avian influenza viruses. The animal studies for the third year have been delayed due to the NADC's response to the 2009 pandemic H1N1.
Impacts
(N/A)
Publications
|
Progress 10/01/07 to 09/30/08
Outputs
Progress Report Objectives (from AD-416) 1) Pathogenesis of avian inluenza virus isolates in swine; 2) Role of avian polymerases in adaptation of swine influenza viruses to swine; 3) Genetic characterization of swine and avian influenza viruses to swine; and 4) Preparation of reagents. Approach (from AD-416) 1) Pathogenesis of avian influenza virus isolates in swine will be evaluated after inoculation into a group of four week old pigs. Microscopic and macroscopic lung lesions and viral replication in lungs and nasal cavities will be determined. 2) Various reassortant viruses containing avian and/or swine polymerase genes will be established using reverse genetics approaches. These reassortant viruses will be tested for their pathogenic potential in swine. 3) Swine and avian influenza isolates will be genetically characterized using conventional sequencing approaches. 4) Hyperimmune sera and various viruses will be made available as reagents. Significant Activities that Support Special Target Populations This is the first year of a 7 year project that is part of a multi- institutional grant. The National Animal Disease Center's role in this grant is to study molecular mechanisms by which influenza viruses acquire increased pathogenicity for humans and animals, and determination of the molecular mechanisms responsible for the transmission of influenza viruses between animals, between humans, and from animals to humans. Initial studies have focused on in vitro analysis of the swine influenza virus polymerase complex. This research addresses NP103 � Animal Health Action Plan Components: 3. Zoonotic diseases and 4. Respiratory diseases. Methods for monitoring this project include email and site visitation.
Impacts
(N/A)
Publications
|
|