Understanding the HIV coreceptor switch from a dynamical perspective.

BMC Evolutionary Biology
Christel Kamp

Abstract

The entry of HIV into its target cells is facilitated by the prior binding to the cell surface molecule CD4 and a secondary coreceptor, mostly the chemokine receptors CCR5 or CXCR4. In early infection CCR5-using viruses (R5 viruses) are mostly dominant while a receptor switch towards CXCR4 occurs in about 50% of the infected individuals (X4 viruses) which is associated with a progression of the disease. There are many hypotheses regarding the underlying dynamics without yet a conclusive understanding. While it is difficult to isolate key factors in vivo we have developed a minimal in silico model based on the approaches of Nowak and May to investigate the conditions under which the receptor switch occurs. The model allows to investigate the evolution of viral strains within a probabilistic framework along the three stages of disease from primary and latent infection to the onset of AIDS with a a sudden increase in viral load which goes along with the impairment of the immune response. The model is specifically applied to investigate the evolution of the viral quasispecies in terms of R5 and X4 viruses which directly translates into the composition of viral load and consequently the question of the coreceptor switch. The model c...Continue Reading

References

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Dec 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Marta CatalfamoH Clifford Lane

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Citations

Oct 6, 2012·Retrovirology·Herwig KoppensteinerMichael Schindler
Aug 2, 2012·Phytotherapy Research : PTR·Long FengGuo-Qiang Zhao
Feb 6, 2014·Journal of Evolutionary Biology·J da Silva, S K Wyatt
Nov 7, 2019·Journal of Virology·Lisa J HendersonAvindra Nath
Aug 2, 2017·Journal of Mathematical Biology·Edna Chilenje Manda, Faraimunashe Chirove

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Software Mentioned

: RungeKutta
PERL
Math
Math RungeKutta

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