Download Estimating minimum host population size for Varicella zoster virus

Project plan, M.Sc. Thesis in Bioinformatics
Estimating minimum host population size for Varicella zoster virus
given different assumptions of reinfections
Supervisors
Peter Norberg, PhD
[email protected]
0735-316166
Dept. of Infectious Medicine,
Sahlgrenska Academy
University of Gothenburg
Devdatt Dubhashi, Prof.
Dept. of Computer Science
Chalmers University of Technology
Background
Herpesviruses are ubiquitous pathogens infecting a wide range of animals, including
humans. Nine herpesviruses infect humans, of which herpes simplex Virus type 1 (HSV1), herpes simplex virus type 2 (HSV-2), and varicella zoster virus (VZV) belongs to the
alphaherpesvirinae subfamily. VZV causes chickenpox at primary infection and establish
lifelong latency in sensory and trigeminal ganglia. Later in life, the virus may reactivate
to cause herpes zoster.
All herpesviruses have been thought to evolve with a relatively constant
evolutionary clock. Phylogenetic studies have demonstrated that clinical HSV-1 strains
can be divided into at least three evolutionary clades [1], and that VZV can be divided
into at least six evolutionary clades [2-4]. However, recent phylogenetic studies suggest
that the evolutionary clock may differ drastically between VZV and HSV-1. Although
these two viruses are highly similar genetically and phenotypically with similar genetic
machineries for replication and miss-match repair, the internal branch lengths are
significantly longer for HSV-1 than for VZV. We have suggested that the underlying
reasons explaining these differences does not depend on differences in times since the
most recent common ancestor, nor in proof-reading capacity [5]. Instead, these
differences likely depend on different numbers of replication cycles per year for HSV-1
and VZV. We believe that the VZV infection always can be described in cycles. That is,
primary infection (chicken pox) –> latency for many year (~60 years) -> reactivation
(Zoster), which triggers a new chicken pox outbreak (primary infection) -> latency ->….
The different branch lengths would thus be explained by different durations of latency
periods for HSV-1 and VZV, and frequencies of reactivation. The general apprehension
has been that the virus is continuously spreading chicken pox -> chicken pox, with only
sporadic activations from zoster. However, we believe that the size of the host
populations (humans) is, and more importantly, has been, far too small to sustain
continuously spreading chicken pox outbreaks other than for very short periods,
infecting relatively few persons. Instead, we believe that latency followed by
reactivation (when new susceptible hosts have been born) is essential for the survival of
VZV.
Project plan, M.Sc. Thesis in Bioinformatics
Purpose
The main purpose of this project is to create an epidemiological model that can be
used to estimate the minimum host population size needed for VZV to survive, with and
without reactivation (Zoster). The minimum host population size can be used to
determine if the reactivation (Zoster) has been necessary for the virus to survive. It may
also have relevance for predictions of future evolution of VZV, particularly in large cities.
Methodology
This project will look at existing epidemiological models, and adapt/improve them
in order to implement a new model for Varicella that can also model reinfections from
Zoster. The new model will be used to investigate which host population sizes that are
required to sustain the disease, with and without reactivation.
References
1.
2.
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4.
5.
Norberg, P., et al., Phylogenetic analysis of clinical herpes simplex virus type 1
isolates identified three genetic groups and recombinant viruses. J Virol, 2004.
78(19): p. 10755-64.
Norberg, P., et al., Complete-genome phylogenetic approach to varicella-zoster
virus evolution: genetic divergence and evidence for recombination. J Virol, 2006.
80(19): p. 9569-76.
Peters, G.A., et al., A full-genome phylogenetic analysis of varicella-zoster virus
reveals a novel origin of replication-based genotyping scheme and evidence of
recombination between major circulating clades. J Virol, 2006. 80(19): p. 9850-60.
Norberg, P., et al., Recombination of Globally Circulating Varicella Zoster Virus. J
Virol, 2015.
Norberg, P., et al., A genome-wide comparative evolutionary analysis of herpes
simplex virus type 1 and varicella zoster virus. PLoS One, 2011. 6(7): p. e22527.