Alternating Host Cell Tropism Shapes the Persistence, Evolution and Coexistence of Epstein–Barr Virus Infections in Human

Huynh, Giao T.; Adler, Frederick R.

doi:10.1007/s11538-010-9590-8

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…31 Given the sequence similarity between hIL-10 and ebvIL-10, changes in the signal peptide of ebvIL-10 could also have an effect on ebvIL-10 protein translocation or signal peptide production. 36 With increasing availability of nextgeneration sequencing, whole-genome analysis of EBV strains isolated from patients with MS will likely provide greater insights into whether genetic variation in the EBV genome is associated with MS, or whether the potential biological impact of EBV in MS is independent of EBV genetics but perhaps related to host immune responses to EBV. EBV LMP-1 is another example of an EBV-encoded immunomodulatory protein.…”

Section: Resultsmentioning

confidence: 99%

Epstein-Barr virus in oral shedding of children with multiple sclerosis

Yea¹,

Tellier²,

Chong³

et al. 2013

Neurology

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Section: Resultsmentioning

confidence: 99%

Epstein-Barr virus in oral shedding of children with multiple sclerosis

Yea¹,

Tellier²,

Chong³

et al. 2013

Neurology

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“…A complicating but very interesting issue that arises is the possible role of epithelial cells in abrogating the sterilizing effect of neutralizing antibody. It is known that antibody that neutralizes B-cell infection actually favors epithelial cell infection [47], thus giving a positive feedback loop in response to neutralizing antibody (for modeling of this effect see [24]). …”

Section: Discussionmentioning

confidence: 99%

“…However, unlike the direct infection model it is sufficiently detailed for mathematical testing and analysis [20], [21], [22], [23], [24], [25], [26]. Mathematical approaches to studying host-pathogen interactions have increased steadily in the last four decades.…”

Section: Introductionmentioning

confidence: 99%

The Cycle of EBV Infection Explains Persistence, the Sizes of the Infected Cell Populations and Which Come under CTL Regulation

et al. 2013

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Previous analysis of Epstein-Barr virus (EBV) persistent infection has involved biological and immunological studies to identify and quantify infected cell populations and the immune response to them. This led to a biological model whereby EBV infects and activates naive B-cells, which then transit through the germinal center to become resting memory B-cells where the virus resides quiescently. Occasionally the virus reactivates from these memory cells to produce infectious virions. Some of this virus infects new naive B-cells, completing a cycle of infection. What has been lacking is an understanding of the dynamic interactions between these components and how their regulation by the immune response produces the observed pattern of viral persistence. We have recently provided a mathematical analysis of a pathogen which, like EBV, has a cycle of infected stages. In this paper we have developed biologically credible values for all of the parameters governing this model and show that with these values, it successfully recapitulates persistent EBV infection with remarkable accuracy. This includes correctly predicting the observed patterns of cytotoxic T-cell regulation (which and by how much each infected population is regulated by the immune response) and the size of the infected germinal center and memory populations. Furthermore, we find that viral quiescence in the memory compartment dictates the pattern of regulation but is not required for persistence; it is the cycle of infection that explains persistence and provides the stability that allows EBV to persist at extremely low levels. This shifts the focus away from a single infected stage, the memory B-cell, to the whole cycle of infection. We conclude that the mathematical description of the biological model of EBV persistence provides a sound basis for quantitative analysis of viral persistence and provides testable predictions about the nature of EBV-associated diseases and how to curb or prevent them.

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“…Infection of epithelial cells, which was shown to play an important role in virus shedding, has not been included in these models. In our previous work, we developed mathematical models of within-host dynamics to study EBV long-term infection, the effect of switching infection between B cells and epithelial cells, the evolution of infection, and the age dependence of EBV associated infectious mononucleosis (Huynh and Adler, 2011a,b). …”

Section: Introductionmentioning

confidence: 99%

Modeling the dynamics of virus shedding into the saliva of Epstein-Barr virus positive individuals

Huynh

Liang

2012

Journal of Theoretical Biology

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Epstein-Barr virus (EBV) can infect both B cells and epithelial cells. Infection of B cells enables the virus to persist within a host while infection of epithelial cells is suggested to amplify viral output. Data from a recent study have shown that the virus shedding in EBV positive individuals is relatively stable over short periods of time but varies significantly over long periods. The mechanisms underlying the regulation of virus shedding within a host are not fully understood. In this paper, we construct a model of ordinary differential equations to study the dynamics of virus shedding into the saliva of infected hosts. Infection of epithelial cells is further separated into infection by virus released from B cells and virus released from epithelial cells. We use the model to investigate whether the long-term variation and short-term stability of virus shedding can be generated by three possible factors: stochastic variations in the number of epithelial cells susceptible to virus released from infected B cells, to virus released from infected epithelial cells, or random variation in the probability that CD8+ T cells encounter and successfully kill infected cells. The results support all three factors to explain the long-term variation but only the first and third factors to explain the short-term stability of virus shedding into saliva. Our analysis also shows that clearance of virus shedding is possible only when there is no virus reactivation from B cells.

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Alternating Host Cell Tropism Shapes the Persistence, Evolution and Coexistence of Epstein–Barr Virus Infections in Human

Cited by 10 publications

References 24 publications

Epstein-Barr virus in oral shedding of children with multiple sclerosis

Epstein-Barr virus in oral shedding of children with multiple sclerosis

The Cycle of EBV Infection Explains Persistence, the Sizes of the Infected Cell Populations and Which Come under CTL Regulation

Modeling the dynamics of virus shedding into the saliva of Epstein-Barr virus positive individuals

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