Giuseppe
Emeritus
J Virol.. [Epub ahead of print]
The NS-segment of an H5N1 highly pathogenic avian influenza virus (HPAIV) is sufficient to alter Replication Efficiency, cell tropism and host range of an H7N1 HPAIV.
Ma W, Brenner D, Wang Z, Dauber B, Ehrhardt C, H?gner K, Herold S, Ludwig S, Wolff T, Yu K, Richt JA, Planz O, Pleschka S. - Institute of Medical Virology, Justus-Liebig-University, D-35392 Giessen, Germany; Robert-Koch-Institute, P15, Nordufer 20, D-13353 Berlin, Germany; Institute for Molecular Virology, Westf?lische-Wilhelms-University, von-Esmarch Str. 56, D-48149 M?nster, Germany; Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Infectious Diseases, Justus-Liebig-University, Giessen, Germany; Harbin Veterinary Research Institute, Harbin 150001, P.R. China; Institute for Virology, Justus-Liebig-University, D-35392 Giessen, Germany; Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Institute for Immunology, Paul-Ehrlich Str. 28, D-72076 T?bingen, Germany.
A reassortant avian influenza virus (FPV NS GD), carrying the NS-segment of the highly pathogenic avian influenza virus (HPAIV) strain A/Goose/Guangdong/1/96 (H5N1) in the genetic background of the HPAIV strain A/FPV/Rostock/34 (H7N1), was rescued by reverse genetics. Remarkably, in contrast to the recombinant wild type FPV (rFPV), the reassortant virus was able to replicate more efficiently in different human cell lines and primary mouse epithelia cells without prior adaptation. Moreover, FPV NS GD caused disease and death in experimentally infected mice and was detected in mouse lungs; in contrast, rFPV was not able to replicate in mice effectively. These results indicated an altered host range and increased virulence. Furthermore FPV NS GD showed pronounced pathogenicity in chicken embryos. In an attempt to define the molecular basis for the apparent differences, we determined that NS1 protein of the H5N1 and H7N1 strains bound the antiviral kinase PKR and the F2F3 domain of CPSF30 with comparable efficiencies in vitro. However, FPV NS GD infection resulted in (i) increased expression of NS1, (ii) faster and stronger PKR inhibition and (iii) stronger IFN-beta-promoter inhibition than rFPV. Taken together, the results shed further light on the importance of the NS segment of a H5N1-strain for viral replication, molecular pathogenicity and host range of HPAIVs and the possible consequences of a reassortment between naturally occurring H7- and H5-type HPAIV.
PMID: 20007264 [PubMed - as supplied by publisher]
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The NS-segment of an H5N1 highly pathogenic avian influenza virus (HPAIV) is sufficient to alter Replication Efficiency, cell tropism and host range of an H7N1 HPAIV.
Ma W, Brenner D, Wang Z, Dauber B, Ehrhardt C, H?gner K, Herold S, Ludwig S, Wolff T, Yu K, Richt JA, Planz O, Pleschka S. - Institute of Medical Virology, Justus-Liebig-University, D-35392 Giessen, Germany; Robert-Koch-Institute, P15, Nordufer 20, D-13353 Berlin, Germany; Institute for Molecular Virology, Westf?lische-Wilhelms-University, von-Esmarch Str. 56, D-48149 M?nster, Germany; Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Infectious Diseases, Justus-Liebig-University, Giessen, Germany; Harbin Veterinary Research Institute, Harbin 150001, P.R. China; Institute for Virology, Justus-Liebig-University, D-35392 Giessen, Germany; Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Institute for Immunology, Paul-Ehrlich Str. 28, D-72076 T?bingen, Germany.
A reassortant avian influenza virus (FPV NS GD), carrying the NS-segment of the highly pathogenic avian influenza virus (HPAIV) strain A/Goose/Guangdong/1/96 (H5N1) in the genetic background of the HPAIV strain A/FPV/Rostock/34 (H7N1), was rescued by reverse genetics. Remarkably, in contrast to the recombinant wild type FPV (rFPV), the reassortant virus was able to replicate more efficiently in different human cell lines and primary mouse epithelia cells without prior adaptation. Moreover, FPV NS GD caused disease and death in experimentally infected mice and was detected in mouse lungs; in contrast, rFPV was not able to replicate in mice effectively. These results indicated an altered host range and increased virulence. Furthermore FPV NS GD showed pronounced pathogenicity in chicken embryos. In an attempt to define the molecular basis for the apparent differences, we determined that NS1 protein of the H5N1 and H7N1 strains bound the antiviral kinase PKR and the F2F3 domain of CPSF30 with comparable efficiencies in vitro. However, FPV NS GD infection resulted in (i) increased expression of NS1, (ii) faster and stronger PKR inhibition and (iii) stronger IFN-beta-promoter inhibition than rFPV. Taken together, the results shed further light on the importance of the NS segment of a H5N1-strain for viral replication, molecular pathogenicity and host range of HPAIVs and the possible consequences of a reassortment between naturally occurring H7- and H5-type HPAIV.
PMID: 20007264 [PubMed - as supplied by publisher]
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