Coreceptor Switching in HIV-1 Subtype B and Subtype C |
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Authors: | T Mugwagwa G Witten |
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Institution: | (1) Department of Mathematics and Applied Mathematics, University of Cape Town, Rondebosch, 7701 Cape Town, South Africa;(2) Stellenbosch Institute for Advanced Study, 19 Jonkershoek Road, Mostertsdrift, Stellenbosch, 7600, South Africa |
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Abstract: | We use a mathematical model to determine the factors affecting the delayed or rare coreceptor switch in HIV-1 subtype C infected
individuals. The model takes into account the two main target cells for the CXCR4-tropic and CCR5-tropic virus and includes
the the lytic and non-lytic immune responses. Computer-based simulations and a sensitivity analysis of the model predict that
a persistent immune response suppresses the CXCR4-tropic virus to low levels and hence preventing a phenotypic switch. However,
not only should the immune response be persistent, but it should have an efficient lytic immune response rather that an efficient
non-lytic response. In addition, we also find that the availability of macrophage cells and enhanced viral kinetics are also
crucial for the dominance of the R5 strain. We suggest that an altered host environment probably as a result of immune activation
may explain the difference in coreceptor switching kinetics between HIV-1 subtype B and subtype C individuals. |
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Keywords: | Coreceptor HIV-1 Subtype Plackett-Burmann Switch |
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