Cytokines in the Pathogenesis of Highly Virulent Influenza Viruses in Humans

Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene

Journal of General Virology ◽

10.1099/vir.0.015727-0 ◽

2009 ◽

Vol 90 (12) ◽

pp. 2990-2994 ◽

Cited By ~ 38

Author(s):

Georg Kochs ◽

Luis Martínez-Sobrido ◽

Stefan Lienenklaus ◽

Siegfried Weiss ◽

Adolfo García-Sastre ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Influenza Viruses ◽

Ns1 Protein ◽

Efficient Induction ◽

Ns1 Gene ◽

Mouse Lungs ◽

Highly Virulent ◽

Complete Deletion

Influenza viruses lacking the interferon (IFN)-antagonistic non-structural NS1 protein are strongly attenuated. Here, we show that mutants of a highly virulent variant of A/PR/8/34 (H1N1) carrying either a complete deletion or C-terminal truncations of NS1 were far more potent inducers of IFN in infected mice than NS1 mutants derived from standard A/PR/8/34. Efficient induction of IFN correlated with successful initial virus replication in mouse lungs, indicating that the IFN response is boosted by enhanced viral activity. As the new NS1 mutants can be handled in standard biosafety laboratories, they represent convenient novel tools for studying virus-induced IFN expression in vivo.

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Generation of a Highly Pathogenic Avian Influenza A Virus from an Avirulent Field Isolate by Passaging in Chickens

Journal of Virology ◽

10.1128/jvi.75.9.4439-4443.2001 ◽

2001 ◽

Vol 75 (9) ◽

pp. 4439-4443 ◽

Cited By ~ 105

Author(s):

Toshihiro Ito ◽

Hideo Goto ◽

Eiji Yamamoto ◽

Hiroko Tanaka ◽

Mutsuko Takeuchi ◽

...

Keyword(s):

Avian Influenza ◽

Influenza A ◽

Field Isolate ◽

Influenza Viruses ◽

Highly Pathogenic ◽

Avian Influenza A Virus ◽

Highly Virulent ◽

Type Sequence ◽

Wild Waterfowl ◽

Selection Of

ABSTRACT Highly virulent avian influenza viruses can arise from avirulent strains maintained in poultry, but evidence to support their generation from viruses in wild birds is lacking. The most likely mechanism for the acquisition of virulence by benign avian viruses is the introduction of mutations by error-prone RNA polymerase, followed by the selection of virulent viruses. To investigate whether this mechanism could apply to wild waterfowl, we studied an avirulent wild-swan virus that replicates poorly in chickens. After 24 consecutive passages by air sac inoculation, followed by five passages in chicken brain, the avirulent virus became highly pathogenic in chickens, producing a 100% mortality rate. Sequence analysis at the hemmaglutinin cleavage site of the original isolate revealed a typical avirulence type of sequence, R-E-T-R, which progressed incrementally to a typical virulence type of sequence, R-R-K-K-R, during repeated passages in chickens. These results demonstrate that avirulent viruses maintained in wild waterfowl in nature and bearing the consensus avirulence type sequence R-E-T-R have the potential to become highly pathogenic while circulating in chickens.

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