Evolutionary history, cross-species transmission and host adaptation of human viruses and their primate homologues
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Date
28/11/2014Author
Lyons, Sinead Mary Kathleen
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Abstract
At present the origins of major human pathogens associated with hepatic disease are
poorly understood. The absence of such information pertaining to the evolutionary history
of hepatitis B virus (HBV) and hepatitis C virus (HCV) and its genetically related viruses
impacts upon the development of vaccines and effective eradication strategies. Studies are
currently limited by the absence of historical samples from which to date the emergence of
human infections and therefore the evolution of human hepatic viruses relies on
epidemiological studies and genetic analysis of contemporary virus populations
worldwide.
Approximately one third of the world’s population is infected with HBV, and despite the
availability of a vaccine, the virus is attributed with over 1 million deaths per year through
liver disease. HBV variants infecting humans show genetic and antigenic heterogeneity
and are currently classified into 8 genotypes A-H with nucleotide divergence of between
9-13%. In addition to these variants, recombination has been detected between genotypes
A and D, and B and C, which can generate novel variants. The past 10 years has seen the
detection of HBV in chimpanzees, gorillas and other non-human primates (NHPs) at
frequencies comparable to those observed in regions of endemic human HBV infection.
Despite the genetic divergence between human and NHP HBV variants the detection of
recombination between human genotype C and chimpanzee and gibbon variants suggests
that HBV can share hosts in nature. The evolutionary process that may have given rise to
the distinct species-specific variants of NHP HBV within overlapping geographical
regions has not been reconciled, with evidence supporting both allopatric speciation and
co-speciation.
HCV a member of the Flaviviridae family currently infects approximately 3% of the
world’s population and is one of the major causes of chronic liver disease, hepatocellular
carcinoma and liver cirrhosis. Human pegivirus (HPgV) a member of the Pegivirus genus
of the Flaviviridae family infects approximately 5% of the world’s population, although it
is of unknown disease association. Very recently, several studies of wild rodent and bat
populations have revealed much greater viral diversity of members of both Hepacivirus
and Pegivirus genera. Homologues of HCV have been detected in a range of species
including domestic dogs (canine hepacivirus [CHV]) and horses (non-primate
hepaciviruses [NPHV]). Similarly, several new pegiviruses have been described in horses
(equine pegivirus, [EPgV] and Theiler’s Disease Associated Virus [TDAV]), several
species of rodents (rodent pegivirus [RPgV]), and further species of bats (bat pegivirus,
[BPgV]). Despite the differences in pathogenicity between HCV and HPgV
infections, they share similar genomic organisation and are capable of establishing
persistent infections in humans. Studies into bat, horse and rodent homologs of HCV
and HPgV have yet to determine disease associations, transmission routes and
seroprevalence.
Studies presented within this thesis broaden our understanding of the clinical
presentations and host range of NPHV and EPgV. Screening to determine the level
of active and past infection to both viruses provides novel insight into infection
frequencies, host range, disease progression and examines the correlation between
infections and the presence or absence of hepatic disease. Research examining HBV
variants circulating in NHPs in Cameroon provides novel evidence for the
occurrence of recombination and cross species transmission between NHP variants
of HBV and examines the role these findings play in expanding our understanding of
the evolution of HBV.