Details:

Alternative Title:
PLoS One
Personal Author:
Schat, Karel A. ; Bingham, John ; Butler, Jeff M. ; Chen, Li-Mei ; Lowther, Sue ; ... More +
Schat, Karel A. ; Bingham, John ; Butler, Jeff M. ; Chen, Li-Mei ; Lowther, Sue ; Crowley, Tamsyn M. ; Moore, Robert J. ; Donis, Ruben O. ; Lowenthal, John W. Less -
Description:
Highly pathogenic H5N1 avian influenza viruses have caused major disease outbreaks in domestic and free-living birds with transmission to humans resulting in 59% mortality amongst 564 cases. The mutation of the amino acid at position 627 of the viral polymerase basic-2 protein (PB2) from glutamic acid (E) in avian isolates to lysine (K) in human isolates is frequently found, but it is not known if this change affects the fitness and pathogenicity of the virus in birds. We show here that horizontal transmission of A/Vietnam/1203/2004 H5N1 (VN/1203) virus in chickens and ducks was not affected by the change of K to E at PB2-627. All chickens died between 21 to 48 hours post infection (pi), while 70% of the ducks survived infection. Virus replication was detected in chickens within 12 hours pi and reached peak titers in spleen, lung and brain between 18 to 24 hours for both viruses. Viral antigen in chickens was predominantly in the endothelium, while in ducks it was present in multiple cell types, including neurons, myocardium, skeletal muscle and connective tissues. Virus replicated to a high titer in chicken thrombocytes and caused upregulation of TLR3 and several cell adhesion molecules, which may explain the rapid virus dissemination and location of viral antigen in endothelium. Virus replication in ducks reached peak values between 2 and 4 days pi in spleen, lung and brain tissues and in contrast to infection in chickens, thrombocytes were not involved. In addition, infection of chickens with low pathogenic VN/1203 caused neuropathology, with E at position PB2-627 causing significantly higher infection rates than K, indicating that it enhances virulence in chickens.
Subject:
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Amino Acids
Animals
Antigens, Viral
Binding Sites
Blood Platelets
Chickens
Ducks
Hemagglutinin Glycoproteins, Influenza Virus
Influenza A Virus, H5N1 Subtype
Influenza In Birds
RNA Replicase
Structure-Activity Relationship
Up-Regulation
Viral Proteins
Virulence
Virus Shedding

Source:
PLoS One. 2012; 7(2).
Document Type:
Journal Article
Collection(s):
CDC Public Access
Main Document Checksum:
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urn:sha256:21946f16b25acae35901898a83cb819f622aab8cf3098e6897cbc7cfc5ec8218
File Type:

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