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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
The role of cells refractory to productive infection in acute hepatitis B viral dynamics
Proceedings of the National Academy of Sciences of the United States of America, Volume 104, No. 12, Year 2007
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Description
During acute hepatitis B virus (HBV) infection viral loads reach high levels (≈1010 HBV DNA per ml), and nearly every hepatocyte becomes infected. Nonetheless, ≈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. © 2007 by The National Academy of Sciences of the USA.
Authors & Co-Authors
Ribeiro, Ruy M.
United States, Los Alamos
Los Alamos National Laboratory
Dusheiko, Geoffrey M.
United Kingdom, London
Ucl Medical School
Perelson, Alan S.
United States, Santa fe
Santa fe Institute
United States, Los Alamos
Los Alamos National Laboratory
Statistics
Citations: 124
Authors: 3
Affiliations: 4
Identifiers
Doi:
10.1073/pnas.0603626104
ISSN:
00278424
Research Areas
Genetics And Genomics
Infectious Diseases