Evolutionary Dynamics of Local Pandemic H1N1/2009 Influenza Virus Lineages Revealed by Whole-Genome Analysis

Baillie, Gregory J.; Galiano, Mónica; Agapow, Paul‐Michael; Chiam, Rachael; Gall, Astrid; Palser, Anne L.; Watson, Simon J.; Hedge, Jessica; Underwood, Anthony; McLean, Estelle; Pebody, Richard; Rambaut, Andrew; Green, Jonathan; Daniels, Rod S.; Pybus, Oliver G.; Kellam, Paul; Zambon, Maria

doi:10.1128/jvi.05347-11

Cited by 108 publications

(114 citation statements)

References 24 publications

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“…H1N1 influenza virus (strain A/England/195/2009) was grown in Madin-Darby canine kidney (MDCK) cells in serum-free DMEM supplemented with 1 g/ml trypsin. The H1N1 influenza virus strain used (A/England/195/2009) was isolated by Public Health England in the United Kingdom in April 2009 (22). The virus was harvested 3 days after inoculation and stored at Ϫ80°C.…”

Section: Methodsmentioning

confidence: 99%

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

Russell

McDonald

Lambert

et al. 2016

J Virol

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Neonates are at a high risk of infection, but vaccines are less effective in this age group; tailored adjuvants could potentially improve vaccine efficacy. Increased understanding about danger sensing by the innate immune system has led to the rational design of novel adjuvants. But differences in the neonatal innate immune response, for example, to Toll-like receptor (TLR) agonists, can reduce the efficacy of these adjuvants in early life. We therefore targeted alternative danger-sensing pathways, focusing on a range of compounds described as inflammasome agonists, including nanoscale silicon dioxide (NanoSiO2), calcium pyrophosphate dihydrate (CPPD) crystals, and muramyl tripeptide (M-Tri-DAP), for their ability to act as adjuvants. In vitro, these compounds induced an interleukin 1-beta (IL-1␤) response in the macrophage-like cell line THP1. In vivo, adult CB6F1 female mice were immunized intramuscularly with H1N1 influenza vaccine antigens in combination with NanoSiO2, CPPD, or M-Tri-DAP and subsequently challenged with H1N1 influenza virus (A/England/195/2009). The adjuvants boosted anti-hemagglutinin IgG and IgA antibody levels. Both adult and neonatal animals that received NanoSiO2-adjuvanted vaccines lost significantly less weight and recovered earlier after infection than control animals treated with antigen alone. Administration of the adjuvants led to an influx of activated inflammatory cells into the muscle but to little systemic inflammation measured by serum cytokine levels. Blocking IL-1␤ or caspase 1 in vivo had little effect on NanoSiO2 adjuvant function, suggesting that it may work through pathways other than the inflammasome. Here we demonstrate that NanoSiO2 can act as an adjuvant and is effective in early life. IMPORTANCEVaccines can fail to protect the most at-risk populations, including the very young, the elderly, and the immunocompromised. There is a gap in neonatal immunity between the waning of maternal protection and routine infant immunization schedules, exacerbated by the failure of vaccines to work in the first months of life. One approach is to design age-specific formulations, with more-effective adjuvants, based on our understanding of the nature of the neonatal immune response. We chose to target the inflammasome, a molecular complex capable of detecting infection and cell damage and of triggering IL-1␤-driven inflammation. We screened a range of compounds in vitro and in vivo and identified three lead candidates: NanoSiO2, CPPD, and MTri-DAP. Of these, NanoSiO2 was the most effective and boosted the anti-influenza virus response in both adult and neonatal mice. This finding is important for the development of age-specific vaccines, designed using our knowledge of the neonatal immune response. Infants bear the brunt of mortality and morbidity from infectious diseases, with 36% of the annual 3.3 million deaths in newborn children caused by infections (1). Influenza virus infection is especially prevalent in early life, with high rates of hospitalization (50 to 100 cases ...

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Section: Methodsmentioning

confidence: 99%

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

Russell

McDonald

Lambert

et al. 2016

J Virol

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“…Although some global phylogenetic analyses have suggested that a stable influenza virus source population could exist in tropical regions such as East and Southeast Asia [3,4], more recent regional studies focused on Hong Kong and southern China have not yielded convincing evidence of viral persistence in these localities, nor of the consistently higher levels of circulating genetic diversity expected of a source population [6,7] (figure 2). Finally, while small chains of influenza A/H1N1 transmission persisted between the summer and autumn waves of the 2009 pandemic in the UK [26], the time interval between waves was unusually short, such that they are unlikely to represent a general phenomenon.…”

Section: (A) Viral Persistencementioning

confidence: 99%

Contrasting the epidemiological and evolutionary dynamics of influenza spatial transmission

Viboud

Nelson

Tan

et al. 2013

Phil. Trans. R. Soc. B

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One contribution of 18 to a Discussion Meeting Issue 'Next-generation molecular and evolutionary epidemiology of infectious disease'. In the past decade, rapid increases in the availability of high-resolution molecular and epidemiological data, combined with developments in statistical and computational methods to simulate and infer migration patterns, have provided key insights into the spatial dynamics of influenza A viruses in humans. In this review, we contrast findings from epidemiological and molecular studies of influenza virus transmission at different spatial scales. We show that findings are broadly consistent in large-scale studies of interregional or inter-hemispheric spread in temperate regions, revealing intense epidemics associated with multiple viral introductions, followed by deep troughs driven by seasonal bottlenecks. However, aspects of the global transmission dynamics of influenza viruses are still debated, especially with respect to the existence of tropical source populations experiencing high levels of genetic diversity and the extent of prolonged viral persistence between epidemics. At the scale of a country or community, epidemiological studies have revealed spatially structured diffusion patterns in seasonal and pandemic outbreaks, which were not identified in molecular studies. We discuss the role of sampling issues in generating these conflicting results, and suggest strategies for future research that may help to fully integrate the epidemiological and evolutionary dynamics of influenza virus over space and time.

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“…The rapidity of evolution, in combination with the increasing availability of genome-scale sequence data and new computational tools for phylogenetic analysis, facilitate the inference of the evolutionary history and spatial spread of IAVs, in turn providing a better understanding of the patterns and processes that underpin epidemics (2)(3)(4)(5)(6)(7)(8). Eighteen antigenically distinct hemagglutinin (HA) subtypes of influenza viruses have been identified to date (9,10).…”

mentioning

confidence: 99%

Emergence of a Highly Pathogenic Avian Influenza Virus from a Low-Pathogenic Progenitor

Monne

Fusaro

Nelson

et al. 2014

J Virol

128

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Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high-and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties. IMPORTANCEThe Italian H7 AI epidemic of 1999 to 2001 was one of the most important AI outbreaks described in Europe. H7 viruses have the ability to evolve into HP forms from LP precursors, although the mechanisms underlying this evolutionary transition are only poorly understood. We combined epidemiological information, whole-genome sequence data, and ultradeep sequencing approaches to provide the most complete characterization of the evolution of HPAI from LPAI viruses undertaken to date. Our analysis revealed that the LPAI viruses were the direct ancestors of the HPAI strains and identified low-frequency minority variants with HPAI mutations that were present in the LPAI samples. Spatial analysis provided key information for the design of effective control strategies for AI at both local and global scales. Overall, this work highlights the importance of implementing rapid eradication measures to prevent the emergence of novel influenza viruses with severe pathogenic properties.

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Evolutionary Dynamics of Local Pandemic H1N1/2009 Influenza Virus Lineages Revealed by Whole-Genome Analysis

Cited by 108 publications

References 24 publications

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

Contrasting the epidemiological and evolutionary dynamics of influenza spatial transmission

Emergence of a Highly Pathogenic Avian Influenza Virus from a Low-Pathogenic Progenitor

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