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Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5050-5. Epub 2007 Mar 14.

The role of cells refractory to productive infection in acute hepatitis B viral dynamics.

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1
Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87507, USA.

Abstract

During acute hepatitis B virus (HBV) infection viral loads reach high levels ( approximately 10(10) HBV DNA per ml), and nearly every hepatocyte becomes infected. Nonetheless, approximately 85-95% of infected adults clear the infection. Although the immune response has been implicated in mediating clearance, the precise mechanisms remain to be elucidated. As infection clears, infected cells are replaced by uninfected ones. During much of this process the virus remains plentiful but nonetheless does not rekindle infection. Here, we analyze data from a set of individuals identified during acute HBV infection and develop mathematical models to test the role of immune responses in various stages of early HBV infection. Fitting the models to data we are able to separate the kinetics of the noncytolytic and the cytolytic immune responses, thus explaining the relative contribution of these two processes. We further show that we need to hypothesize that newly generated uninfected cells are refractory to productive infection. Without this assumption, viral resurgence is observed as uninfected cells are regenerated. Such protection, possibly mediated by cytokines, may also be important in resolving other acute viral infections.

PMID:
17360406
PMCID:
PMC1829262
DOI:
10.1073/pnas.0603626104
[Indexed for MEDLINE]
Free PMC Article
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