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

• DOI: 10.1128/jvi.01668-09
• Publication Date: 2009-12-10T01:55:14Z
• Authors: Wenjun Ma; Dominique Brenner; Zhongfang Wang; Bianca Dauber; Christina Ehrhardt; Katrin Högner; Susanne Herold; Stephan Ludwig; Thorsten Wolff; Kangzhen Yu; Jürgen A. Richt; Oliver Planz; Stephan Pleschka
• Keywords: Tissue tropism; Protein kinase R; Reassortment

ABSTRACT A reassortant avian influenza virus (designated FPV NS GD), carrying the NS-segment of highly pathogenic (HPAIV) strain A/Goose/Guangdong/1/96 (GD; H5N1) in genetic background HPAIV A/FPV/Rostock/34 (FPV; H7N1), was rescued by reverse genetics. Remarkably, contrast to recombinant wild-type (rFPV), able replicate more efficiently different human cell lines and primary mouse epithelia cells without prior adaptation. Moreover, GD caused disease death experimentally infected mice detected lungs; contrast, rFPV not effectively. These results indicated an altered host range increased virulence. Furthermore showed pronounced pathogenicity chicken embryos. In attempt define molecular basis for apparent differences, we determined that NS1 proteins H5N1 H7N1 strains bound antiviral kinase PKR F2F3 domain cleavage polyadenylation specificity factor 30 (CPSF30) with comparable efficiencies vitro . However, infection resulted (i) expression NS1, (ii) faster stronger inhibition, (iii) beta interferon promoter inhibition than rFPV. Taken together, shed further light on importance segment viral replication, pathogenicity, HPAIVs possible consequences a reassortment between naturally occurring H7 H5 type HPAIVs.