Phylogenetic analysis of full-length, early infection, hepatitis C virus genomes among people with intravenous drug use: the InC3Study.
Cross-continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3). One hundred and ninety-two full-length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross-continental, full-length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non-Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro-epidemics within geographically isolated communities.
School of Medical Sciences, UNSW, Sydney, NSW, Australia.
C
C
Rodrigo
School of Medical Sciences, UNSW, Sydney, NSW, Australia.
A A
AA
Eltahla
School of Medical Sciences, UNSW, Sydney, NSW, Australia.
R A
RA
Bull
School of Medical Sciences, UNSW, Sydney, NSW, Australia.
F
F
Luciani
The Kirby Institute, UNSW, Sydney, NSW, Australia.
J
J
Grebely
The Kirby Institute, UNSW, Sydney, NSW, Australia.
G J
GJ
Dore
The Kirby Institute, UNSW, Sydney, NSW, Australia.
T
T
Applegate
University of New Mexico, Albuquerque, NM, USA.
K
K
Page
CRCHUM, Université de Montréal, Montreal, QC, Canada.
J
J
Bruneau
University of California, San Francisco, CA, USA.
M D
MD
Morris
Johns Hopkins Medical Institutions, Baltimore, MD, USA.
A L
AL
Cox
Johns Hopkins Medical Institutions, Baltimore, MD, USA.
W
W
Osburn
Harvard Medical School, Boston, MA, USA.
A Y
AY
Kim
CRCHUM, Université de Montréal, Montreal, QC, Canada.
N H
NH
Shoukry
Harvard Medical School, Boston, MA, USA.
G M
GM
Lauer
The Kirby Institute, UNSW, Sydney, NSW, Australia.
L
L
Maher
Academic Medical Center, Amsterdam, The Netherlands.|GGD Public Health Service of Amsterdam, Amsterdam, The Netherlands.
J
J
Schinkel
Academic Medical Center, Amsterdam, The Netherlands.|GGD Public Health Service of Amsterdam, Amsterdam, The Netherlands.
M
M
Prins
Burnet Institute, Melbourne, Vic, Australia.|Monash University, Clayton, Vic, Australia.|Alfred Hospital, Melbourne, Vic, Australia.
M
M
Hellard
School of Medical Sciences, UNSW, Sydney, NSW, Australia.
A R
AR
Lloyd
D000328:Adult; D001315:Australia / Q000453:epidemiology; D055030:Drug Users; D005060:Europe / Q000453:epidemiology; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000453:epidemiology / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D009656:North America / Q000453:epidemiology; D010802:Phylogeny; D010949:Plasma / Q000821:virology; D017422:Sequence Analysis, DNA; D015819:Substance Abuse, Intravenous / Q000150:complications*; D055815:Young Adult
Hepatitis C virus; NGS; molecular epidemiology; people who inject drugs; phylogenetics