Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

Abstract

BackgroundUnderstanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established.ResultsThis study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA) of viral genomes that might correlate with their different phenotypic behavior.ConclusionsThe study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.

The 2009 pandemic (H1N1) viruses isolated from pigs show enhanced pathogenicity in mice

“…Although the difference of amino acids did not match the known functional sites associated with pathogenicity in mice, these novel viruses possessed six common amino acid changes in HA, PA, PB2 and NS1 proteins compared with human 2009/H1N1 strains. Some of the above mutations were similar to the molecular changes of 2009/H1N1 virus reported by other researchers [23,35]. It is reported that the HA, PB2, PA and NS genes of 2009/H1N1 are in the classical swine lineage derived from the 1918 Spanish pandemic virus, and many viral mutations associated with the pathogenicity and cross-species transmission of 2009/H1N1 are present in these viral proteins, e.g., D222G in HA [36], T271A in PB2 [37], T552S in PA [38] and E125D in NS1 [39].…”

“…Many investigators have concentrated on the pathogenicity of 2009/H1N1 isolates in a mice model, and found that most of the tested 2009/H1N1 viruses show low lethality in mice, only at the highest dose of 10 6.5 EID 50 or PFU, though they could cause more severe pathological lesions in lungs than currently seasonal A(H1N1) viruses [14,15,21,22]. Most strikingly, researchers recently isolated some 2009/H1N1 variants with certain amino acid mutations, and infection experiments showed that these variants could induce approximately 40%-100% lethal response in mice even at the lower doses [10,23,24], which indicates that 2009/H1N1 viruses possess a potential phenotypic variability in the evolutionary process.…”

CXCL14 deficiency does not impact the outcome of influenza or Escherichia coli infections in mice

“…Deficiency of CXCL14 does not affect the severity of the infection with either influenza virus or E. coli. CXCL14-deficient and wild type control mice were intranasally infected with A) 10 3 EID 50 of influenza PR8 (n=12 per group), and B) 10 4 EID 50 of influenza A/Mexico/4108/09 (n=12 per group); the weight loss and the survival rate were monitored over the first 14 days post infection. C) Histopathological evaluation of the lung tissue from mice infected with PR8, 6 days post-infection.…”

“…-/-and wildtype C57B6/129 mice (WT) were infected with 10 4 EID 50 of A/Mexico/4108/2009 and 10 3 EID 50 of A/Puerto Rico/8/1934 (ATCC #VR-95) (PR8), as previously described [10].…”

Biological characterization of RNA polymerase proteins from human 2009 pandemic H1N1 and low pathogenic avian H5N2 and H9N2 influenza viruses

“…. A human lung epithelial cell line known as A549 (one of the permissive cell lines to influenza virus infection) has been widely used to study the viral replication kinetics and host response to virus infection (Farooqui et al, 2012;.…”