Dataset Information

Pawelek2016 - Within-Host Models of High and Low Pathogenic Influenza Virus Infections

ABSTRACT: a possible mechanism of MP in determining HP versus LP outcomes, and how different interventions might affect infection dynamics

SUBMITTER: Sarubini Kananathan

PROVIDER: MODEL1812040006 | BioModels | 2020-07-09

REPOSITORIES: BioModels

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Publications

Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages.

Pawelek Kasia A KA Dor Daniel D Salmeron Cristian C Handel Andreas A

PloS one 20160226 2

The World Health Organization identifies influenza as a major public health problem. While the strains commonly circulating in humans usually do not cause severe pathogenicity in healthy adults, some strains that have infected humans, such as H5N1, can cause high morbidity and mortality. Based on the severity of the disease, influenza viruses are sometimes categorized as either being highly pathogenic (HP) or having low pathogenicity (LP). The reasons why some strains are LP and others HP are no ...[more]

PMID: 26918620

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Project description:Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. All 4 challenge groups showed sero-conversion and evidence of virus replication, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes were detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models should be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections.

Dataset Information

Pawelek2016 - Within-Host Models of High and Low Pathogenic Influenza Virus Infections

Publications

Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages.

Similar Datasets

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