PXD003803

PXD003803 is an original dataset announced via ProteomeXchange.

Title	Macaque models for influenza A virus
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.
HostingRepository	PRIDE
AnnounceDate	2016-06-20
AnnouncementXML	Submission_2016-06-20_06:16:31.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD003803
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Stuart Armstrong
SpeciesList	scientific name: Unidentified Influenza A virus (H1N1); NCBI TaxID: 1323429; scientific name: Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey); NCBI TaxID: 9541;
ModificationList	iodoacetamide - site C: 57.021464; monohydroxylated residue: 15.994915
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-17 05:29:10	ID requested
⏵ 1	2016-06-20 06:16:32	announced

Marriott AC, Dennis M, Kane JA, Gooch KE, Hatch G, Sharpe S, Prevosto C, Leeming G, Zekeng EG, Staples KJ, Hall G, Ryan KA, Bate S, Moyo N, Whittaker CJ, Hallis B, Silman NJ, Lalvani A, Wilkinson TM, Hiscox JA, Stewart JP, Carroll MW, Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection. PLoS One, 11(6):e0157887(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: H1N1pdm influenza virus, Intra-nasal challenge, label free proteomics

Prof. Julian A. Hiscox
contact affiliation	Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, UK
contact email	julianh@liverpool.ac.uk
lab head
Stuart Armstrong
contact affiliation	Infection Biology
contact email	sarmstro@liv.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003803
     1. Label: PRIDE project
     2. Name: Macaque models for influenza A virus