Contribution of newly discovered and emerging viruses to human disease
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Nguyen2016.docx (9.096Mb)
Date
29/11/2016Author
Nguyen, Dung Van
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Abstract
According to the World Health Organization, over 200 infectious diseases in humans
originate from animals (zoonoses), posing significant threats to human health.
Zoonotic agents account for the majority of emerging and re-emerging pathogens. The
human-animal interface has been recognised as an important risk factor that facilitates
viruses to cross the species barrier and establish infection in humans. This indicates a
need to perform surveillance of human populations who are at high risk of zoonotic
infection due to their frequent contact with animals, together with the animals to which
humans are exposed. The VIZIONS (Vietnam Initiative on Zoonotic Infections) has
been conducted to directly respond to that need.
The large virus family Picornaviridae include known emerging pathogens that have
major impacts on the economies and human and animal health (e.g. foot-and-mouth
disease virus, hand foot and mouth disease virus). Some enteroviruses (EVs) and
parechoviruses in this family have been shown to be able to infect both humans and
animals while a number of new picornaviruses (new EV variants, cosaviruses,
cardioviruses, hunniviruses) with unknown pathogenicity and zoonotic potential have
been discovered. This thesis, as part of VIZIONS, hopes to address the following gaps
in our knowledge of such viruses in six genera (Enterovirus, Parechovirus, Cosavirus,
Cardiovirus, Kobuvirus and Hunnivirus) of the family Picornaviridae:
1) The prevalence and genetic diversity of picornaviruses in studied samples
2) The epidemiology and disease association of the identified viruses
3) The overlaps (if any) of picornaviruses circulating in animals and humans
4) Possible animal sources of picornavirus infections in humans
In order to do that, over 2,000 faecal samples collected from a wide range of hosts
(pigs, rats, bamboo rats, shrews, bats, chickens, ducks, boars, civets, porcupines,
monkeys and humans) were screened for picornaviruses by nested PCR and real-time
PCR assays. Detection frequencies varied between viruses and sample origins with
kobuvirus as the most commonly detected virus, followed by EV, cardiovirus and
hunnivirus. Parechovirus and cosavirus were not detected.
Comparison of detection frequencies of viruses infecting pigs revealed a disease
(diarrhoea) association with porcine kobuvirus (PKV) but not EV infections. However,
differences in PKV viral loads between diarrhoeic and non-diarrhoeic pigs were not
statistically significant (p = 0.22). In addition, the PKV VP1 sequences from the two
pig categories were not phylogenetically distinct. EV VP1 sequences obtained from
pigs and boars showed high genetic diversity with four previously known types and
nine new types (EV-G8 to -G16). Analyses of complete genome sequences of two new
EV types provided evidence for inter-type recombination with a putative breakpoint
in the 2A coding region.
Similarly, study on samples from monkeys showed endemic infection of EV but no
overlap with EV variants in humans was observed. The majority of EV detected in
monkeys were novel with evidence for chimeric genomes and putative recombination
breakpoints in the 2A region. New criteria for the classification of EV were
additionally proposed.
Characterization by sequencing of VP4/VP2 and VP1 regions or complete genomes of
picornaviruses in rats and bamboo rats also showed relatively high genetic diversity.
While these viruses can infect different species of rats, they were again genetically
different from viruses detected in the studied human populations.
In summary, studies in this thesis provide substantial new information on the
prevalence, genetic diversity and disease association of picornaviruses in the studied
populations. However, picornaviruses detected from animals were consistently
separate from those found in humans, consistent with a relatively limited zoonotic
potential of members of the virus family.
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