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Time-course analysis of main markers of primary infection in cats with the feline immunodeficiency virus.

COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE(2012)

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摘要
Studies of the response of the immune system to feline immunodeficiency virus (FIV) during primary infection have shown that a subpopulation of CD8(+) T-cells with an activated phenotype and reduced expression of the CD8 beta chain (denoted CD8 beta(low) T cells) expands to reach up to 80% of the total CD8+ T cell count. The expansion of this subpopulation is considered to be a signature of FIV and an indicator of immune system alteration. We use a simple mathematical formalism to study the relationships over time between the dose of infection, the size of the CD8 beta(low) population, and the circulating viral load in cats infected with FIV. Viremia profiles are described using a combination of two exponential laws, whereas the CD8 beta(low) percentage (out of the total CD8(+) population) is represented by a Gompertz law including an expansion phase and a saturation phase. Model parameters are estimated with a population approach using data from 102 experimentally infected cats. We examine the dose of infection as a potential covariate of parameters. We find that the rates of increase of viral load and of CD8 beta(low) percentage are both correlated with the dose of infection. Cats that develop strong acute viremia also show the largest degree of CD8 beta(low) expansion. The two simple models are robust tools for analysing the time course of CD8 beta(low) percentage and circulating viral load in FIV-infected cats and may be useful for generating new insights on the disease and on the design of therapeutic strategies, potentially applicable to HIV infection.
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关键词
algorithms,viral load,phenotype,regression analysis
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