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Dynamics of recurrent viral infection.

ABSTRACT: In chronic viral infection, low levels of viral replication and infectious particle production are maintained over long periods, punctuated by brief bursts of high viral production and release. We apply well-established principles of modelling virus dynamics to the study of chronic viral infection, demonstrating that a model which incorporates the distinct contributions of cytotoxic T lymphocytes (CTLs) and antibodies exhibits long periods of quiescence followed by brief bursts of viral production. This suggests that for recurrent viral infections, no special mechanism or exogenous trigger is necessary to provoke an episode of reactivation; rather, the system may naturally cycle through recurrent episodes at intervals which can be many years long. We also find that exogenous factors which cause small fluctuations in the natural course of the infection can trigger a recurrent episode. Our model predicts that longer periods between recurrences are associated with more severe viral episodes. Four factors move the system towards less frequent, more severe episodes: decreased viral infectivity, decreased CTL efficacy, decreased memory T cell response and increased antibody efficacy.

SUBMITTER: Yao W

PROVIDER: S-EPMC1635529 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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Dynamics of recurrent viral infection.

Yao W W Hertel L L Wahl L M LM

Proceedings. Biological sciences 20060901 1598

In chronic viral infection, low levels of viral replication and infectious particle production are maintained over long periods, punctuated by brief bursts of high viral production and release. We apply well-established principles of modelling virus dynamics to the study of chronic viral infection, demonstrating that a model which incorporates the distinct contributions of cytotoxic T lymphocytes (CTLs) and antibodies exhibits long periods of quiescence followed by brief bursts of viral producti ...[more]

PMID: 16901839

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Project description:Epstein-Barr virus (EBV) is a human herpesvirus that causes acute infectious mononucleosis and is associated with cancer and autoimmune disease. While many studies have been performed examining acute disease in adults following primary infection, little is known about the virological and immunological events during EBV's lengthy 6 week incubation period owing to the challenge of collecting samples from this stage of infection. We conducted a prospective study in college students with special emphasis on frequent screening to capture blood and oral wash samples during the incubation period. Here we describe the viral dissemination and immune response in the 6 weeks prior to onset of acute infectious mononucleosis symptoms. While virus is presumed to be present in the oral cavity from time of transmission, we did not detect viral genomes in the oral wash until one week before symptom onset, at which time viral genomes were present in high copy numbers, suggesting loss of initial viral replication control. In contrast, using a sensitive nested PCR method, we detected viral genomes at low levels in blood about 3 weeks before symptoms. However, high levels of EBV in the blood were only observed close to symptom onset-coincident with or just after increased viral detection in the oral cavity. These data imply that B cells are the major reservoir of virus in the oral cavity prior to infectious mononucleosis. The early presence of viral genomes in the blood, even at low levels, correlated with a striking decrease in the number of circulating plasmacytoid dendritic cells well before symptom onset, which remained depressed throughout convalescence. On the other hand, natural killer cells expanded only after symptom onset. Likewise, CD4+ Foxp3+ regulatory T cells decreased two fold, but only after symptom onset. We observed no substantial virus specific CD8 T cell expansion during the incubation period, although polyclonal CD8 activation was detected in concert with viral genomes increasing in the blood and oral cavity, possibly due to a systemic type I interferon response. This study provides the first description of events during the incubation period of natural EBV infection in humans and definitive data upon which to formulate theories of viral control and disease pathogenesis.

Dataset Information

Dynamics of recurrent viral infection.

Publications

Dynamics of recurrent viral infection.

Similar Datasets

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