TY - JOUR
T1 - Bayesian phylogeography and pathogenic characterization of smallpox based on HA, ATI, and crMB genes
AU - Adam, Dillon C.
AU - Scotch, Matthew
AU - MacIntyre, Chandini Raina
N1 - Funding Information:
This work was supported by a grant from the NHRMC Centre for Research Excellence in Integrated Systems for Epidemic Response (ISER) (grant number 1107393) to D.C.A. and C.R.M. This work was also supported by a grant from the tri-university (Arizona State University, King’s College London, and University of New South Wales) PLuS Alliance to M.S. and C.R.M. We would like to acknowledge the support for D.C.A. through an Australian Government Research Training Program Scholarship. The funders had no role in the study’s conception, design, data collection, and interpretation, or the decision to submit the work for publication.
Funding Information:
This work was supported by a grant from the NHRMC Centre for Research Excellence in Integrated Systems for Epidemic Response (ISER) (grant number 1107393) to D.C.A. and C.R.M. This work was also supported by a grant from the tri-university (Arizona State University, King's College London, and University of New South Wales) PLuS Alliance to M.S. and C.R.M. We would like to acknowledge the support for D.C.A. through an Australian Government Research Training Program Scholarship. The funders had no role in the study's conception, design, data collection, and interpretation, or the decision to submit the work for publication.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Variola virus is at risk of re-emergence either through accidental release, bioterrorism, or synthetic biology. The use of phylogenetics and phylogeography to support epidemic field response is expected to grow as sequencing technology becomes miniaturized, cheap, and ubiquitous. In this study, we aimed to explore the use of common VARV diagnostic targets hemagglutinin (HA), cytokine response modifier B (CrmB), and A-type inclusion protein (ATI) for phylogenetic characterization as well as the representativeness of modelling strategies in phylogeography to support epidemic response should smallpox re-emerge. We used Bayesian discrete-trait phylogeography using the most complete data set currently available of whole genome (n ¼ 51) and partially sequenced (n ¼ 20) VARV isolates. We show that multilocus models combining HA, ATI, and CrmB genes may represent a useful heuristic to differentiate between VARV Major and subclades of VARV Minor which have been associated with variable case-fatality rates. Where whole genome sequencing is unavailable, phylogeography models of HA, ATI, and CrmB may provide preliminary but uncertain estimates of transmission, while supplementing whole genome models with additional isolates sequenced only for HA can improve sample representativeness, maintaining similar support for transmission relative to whole genome models. We have also provided empirical evidence delineating historic international VARV transmission using phylogeography. Due to the persistent threat of re-emergence, our results provide important research for smallpox epidemic preparedness in the posteradication era as recommended by the World Health Organisation.
AB - Variola virus is at risk of re-emergence either through accidental release, bioterrorism, or synthetic biology. The use of phylogenetics and phylogeography to support epidemic field response is expected to grow as sequencing technology becomes miniaturized, cheap, and ubiquitous. In this study, we aimed to explore the use of common VARV diagnostic targets hemagglutinin (HA), cytokine response modifier B (CrmB), and A-type inclusion protein (ATI) for phylogenetic characterization as well as the representativeness of modelling strategies in phylogeography to support epidemic response should smallpox re-emerge. We used Bayesian discrete-trait phylogeography using the most complete data set currently available of whole genome (n ¼ 51) and partially sequenced (n ¼ 20) VARV isolates. We show that multilocus models combining HA, ATI, and CrmB genes may represent a useful heuristic to differentiate between VARV Major and subclades of VARV Minor which have been associated with variable case-fatality rates. Where whole genome sequencing is unavailable, phylogeography models of HA, ATI, and CrmB may provide preliminary but uncertain estimates of transmission, while supplementing whole genome models with additional isolates sequenced only for HA can improve sample representativeness, maintaining similar support for transmission relative to whole genome models. We have also provided empirical evidence delineating historic international VARV transmission using phylogeography. Due to the persistent threat of re-emergence, our results provide important research for smallpox epidemic preparedness in the posteradication era as recommended by the World Health Organisation.
KW - Biosecurity
KW - Epidemics
KW - Phylogeography
KW - Public health
KW - Smallpox
KW - Variola virus
UR - http://www.scopus.com/inward/record.url?scp=85056321571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056321571&partnerID=8YFLogxK
U2 - 10.1093/molbev/msy153
DO - 10.1093/molbev/msy153
M3 - Article
C2 - 30099520
AN - SCOPUS:85056321571
SN - 0737-4038
VL - 35
SP - 2607
EP - 2617
JO - Molecular biology and evolution
JF - Molecular biology and evolution
IS - 11
ER -