Non-Mouse-Adapted H1N1pdm09 Virus as a Model for Influenza Research.

Irina Kiseleva,Anastasia Katelnikova,Mohammad Al Farroukh,Ludmila Puchkova,Larisa Rudenko,Andrey Rekstin,Ekaterina Bazhenova

doi:10.3390/v12060590

Abstract

The number of lung-adapted influenza viruses is limited. Most of them are not antigenically related to current circulating viruses. Viruses similar to recent strains are required for screening modern antiviral compounds and studying new vaccine candidates against novel influenza viruses. The process by which an influenza virus adapts to a new host is rather difficult. The aim of this study was to select a non-adapted current virus whose major biological properties correspond to those of classical lab-adapted viruses. Mice were inoculated intranasally with non-lung-adapted influenza viruses of subtype H1N1pdm09. They were monitored closely for body weight loss, mortality outcomes and gross pathology for 14 days following inoculation, as well as viral replication in lung tissue. Lung-adapted PR8 virus was used as a control. The tested viruses multiplied equally well in the lower respiratory tract of mice without prior adaptation but dramatically differed in lethality; the differences in their toxicity and pathogenicity in mice were established. A/South Africa/3626/2013 (H1N1)pdm09 virus was found to be an appropriate candidate to replace PR8 as a model virus for influenza research. No prior adaptation to the animal model is needed to reach the pathogenicity level of the classical mouse-adapted PR8 virus.

Highlights

Influenza A mouse and ferret models are widely used in influenza virus research in, for instance, preclinical studies of vaccine candidates to evaluate their safety, immunogenicity and efficacy in preventing influenza infection; to investigate the pathogenesis of influenza infection; or to screen antiviral compounds [1,2,3,4,5,6,7,8,9,10]
The following influenza A viruses were used: A/South Africa/3626/2013 (H1N1)pdm09 (SA), obtained from The Francis Crick Institute (London, UK); and the A/California/07/2009 (H1N1)pdm09 (CA), obtained from the CDC (Atlanta, GA, USA), CDC ID No 2009712112; A/Singapore/1/57 (H2N2) (SGP) and four mouse-adapted strains—A/Puerto Rico/8/34 (H1N1) (PR8), B/Lee/40 (LEE), A/Victoria/35/72 (H3N2) (VIC), and A/Aichi/2/68 (H3N2) (ACH)—were obtained from the Virus
H1N1pdm09, reference virus of the Asian pandemic of 1957, and PR8) were studied for their capacity to grow at temperatures of 32 ◦ C, 26 ◦ C and 40 ◦ C

Summary

Introduction

Influenza A mouse and ferret models are widely used in influenza virus research in, for instance, preclinical studies of vaccine candidates to evaluate their safety, immunogenicity and efficacy in preventing influenza infection; to investigate the pathogenesis of influenza infection; or to screen antiviral compounds [1,2,3,4,5,6,7,8,9,10]. The pathogenesis of influenza infection has been studied in mice using lab lung-adapted strains [2]. The limited number of classical mouse-adapted viruses includes A/Puerto. All of them are antigenically distinct from currently circulating viruses. A number of tests (for instance, the screening of antiviral agents) require the use of currently circulating strains

Objectives

Methods

Results

Discussion

Conclusion