The onset of virus shedding and clinical signs in chickens infected with high-pathogenicity and low-pathogenicity avian influenza viruses

2008 ◽  
Vol 37 (6) ◽  
pp. 555-577 ◽  
Author(s):  
Anna R. Spickler ◽  
Darrell W. Trampel ◽  
James A. Roth
Keyword(s):  
Avian Influenza ◽  
Clinical Signs ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Virus Shedding ◽  
High Pathogenicity

scholarly journals Amino Acid Residue 217 in the Hemagglutinin Glycoprotein Is a Key Mediator of Avian Influenza H7N9 Virus Antigenicity

2018 ◽  
Vol 93 (1) ◽  
Author(s):  
Pengxiang Chang ◽  
Joshua E. Sealy ◽  
Jean-Remy Sadeyen ◽  
Munir Iqbal
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Immune Escape ◽  
Influenza Viruses ◽  
Single Mutation ◽  
H7n9 Virus ◽  
Avian Influenza Viruses ◽  
Antigenic Analysis ◽  
Neutralizing Capacity ◽  
High Pathogenicity

ABSTRACTAvian influenza viruses continue to evolve and acquire mutations that facilitate antigenic drift and virulence change. In 2017, low-pathogenicity H7N9 avian influenza viruses evolved to a high-pathogenicity phenotype in China. Comparative antigenic analysis of the low- and high-pathogenicity virus strains showed marked variability. In order to identify residues that may be linked to the antigenic change among the H7N9 viruses, we serially passaged the viruses in the presence of homologous ferret antiserum. Progeny viruses able to overcome the neutralizing capacity of the antiserum were sequenced. The analysis showed that the emergent immune escape viruses contained mutations A125T, A151T, and L217Q in the hemagglutinin (HA) glycoprotein as early as passage 5 and that these mutations persisted until passage 10. The results revealed that a single mutation, L217Q, in the HA of H7N9 virus led to 23- and 8-fold reductions in hemagglutination inhibition (HI) titer with ferret and chicken antisera, respectively. Further analysis showed that this change also contributed to antigenic differences between the low- and high-pathogenicity H7N9 viruses, thus playing a major role in their antigenic diversification. Therefore, evolutionary changes at amino acid position 217 in the H7N9 viruses can serve as a genetic marker for virus antigenic diversity during vaccine seed matching and selection. Thein vitroimmune escape mutant selection method used in this study could also aid in the prediction of emerging antigenic variants in naturally infected or immunized animals.IMPORTANCEAvian influenza H7N9 viruses circulating in poultry and wild birds continue to evolve and acquire important phenotypic changes. Mutations to the virus hemagglutinin (HA) glycoprotein can modulate virus antigenicity and facilitate virus escape from natural or vaccine-induced immunity. The focus of this study was to identify evolutionary markers in the HA of H7N9 that drive escape from antibody-based immunity. To achieve this, we propagated low-pathogenicity H7N9 virus in the presence of polyclonal antiserum derived from ferrets infected with the same strain of virus (homologous antiserum). This selection process was repeated 10 times. The HA gene sequences of viruses recovered after the fifth passage showed that the viruses readily acquired mutations at three different amino acid positions (A125T, A151T, and L217Q). Further functional analysis of these mutations confirmed that the mutation at residue 217 in the HA was responsible for mediating changes to the immunological properties of the H7N9 virus.

scholarly journals Insights into the Acquisition of Virulence of Avian Influenza Viruses during a Single Passage in Ferrets

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 915
Author(s):  
Butler ◽  
Middleton ◽  
Haining ◽  
Layton ◽  
Rockman ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Respiratory Tract ◽  
Severe Disease ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Upper Respiratory Tract ◽  
Avian Influenza Viruses ◽  
Single Passage ◽  
H5n1 Isolate ◽  
High Pathogenicity

Circulating avian influenza viruses pose a significant threat, with human infections occurring infrequently but with potentially severe consequences. To examine the dynamics and locale of the adaptation process of avian influenza viruses when introduced to a mammalian host, we infected ferrets with H5N1 viruses. As expected, all ferrets infected with the human H5N1 isolate A/Vietnam/1203/2004 showed severe disease and virus replication outside the respiratory tract in multiple organs including the brain. In contrast infection of ferrets with the avian H5N1 virus A/Chicken/Laos/Xaythiani26/2006 showed a different collective pattern of infection; many ferrets developed and cleared a mild respiratory infection but a subset (25–50%), showed extended replication in the upper respiratory tract and developed infection in distal sites. Virus from these severely infected ferrets was commonly found in tissues that included liver and small intestine. In most instances the virus had acquired the common virulence substitution PB2 E627K but, in one case, a previously unidentified combination of two amino acid substitutions at PB2 S489P and NP V408I, which enhanced polymerase activity, was found. We noted that virus with high pathogenicity adaptations could be dominant in an extra-respiratory site without being equally represented in the nasal wash. Further ferret passage of these mutated viruses resulted in high pathogenicity in all ferrets. These findings illustrate the remarkable ability of avian influenza viruses that avoid clearance in the respiratory tract, to mutate towards a high pathogenicity phenotype during just a single passage in ferrets and also indicate a window of less than 5 days in which treatment may curtail systemic infection.

From low to high pathogenicity-Characterization of H7N7 avian influenza viruses in two epidemiologically linked outbreaks

2018 ◽  
Vol 65 (6) ◽  
pp. 1576-1587 ◽  
Author(s):  
Klaas Dietze ◽  
Annika Graaf ◽  
Timo Homeier-Bachmann ◽  
Christian Grund ◽  
Leonie Forth ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
High Pathogenicity

scholarly journals Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses

2000 ◽  
Vol 74 (3) ◽  
pp. 1443-1450 ◽  
Author(s):  
Jody K. Dybing ◽  
Stacey Schultz-Cherry ◽  
David E. Swayne ◽  
David L. Suarez ◽  
Michael L. Perdue
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Transforming Growth Factor ◽  
Clinical Signs ◽  
Influenza Viruses ◽  
Rapid Weight Loss ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic

ABSTRACT In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in poultry in Hong Kong (HK) and was linked to a direct transmission to humans. The factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza A viruses infecting and causing disease in mammals is not known. In this study, two avian and one human HK-origin H5N1 virus along with four additional highly pathogenic H5 avian influenza viruses were analyzed for their pathogenicity in 6- to 8-week-old BALB/c mice. Both the avian and human HK H5 influenza virus isolates caused severe disease in mice, characterized by induced hypothermia, clinical signs, rapid weight loss, and 75 to 100% mortality by 6 to 8 days postinfection. Three of the non-HK-origin isolates caused no detectable clinical signs. One isolate, A/tk/England/91 (H5N1), induced measurable disease, and all but one of the animals recovered. Infections resulted in mild to severe lesions in both the upper and lower respiratory tracts. Most consistently, the viruses caused necrosis in respiratory epithelium of the nasal cavity, trachea, bronchi, and bronchioles with accompanying inflammation. The most severe and widespread lesions were observed in the lungs of HK avian influenza virus-infected mice, while no lesions or only mild lesions were evident with A/ck/Scotland/59 (H5N1) and A/ck/Queretaro/95 (H5N2). The A/ck/Italy/97 (H5N2) and the A/tk/England/91 (H5N1) viruses exhibited intermediate pathogenicity, producing mild to moderate respiratory tract lesions. In addition, infection by the different isolates could be further distinguished by the mouse immune response. The non-HK-origin isolates all induced production of increased levels of active transforming growth factor β following infection, while the HK-origin isolates did not.

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