Quantitative Biology

, Volume 5, Issue 2, pp 173–182 | Cite as

A systematic analysis of intrinsic regulators for HIV-1 R5 to X4 phenotypic switch

Research Article
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Abstract

Background

Human immunodeficiency virus isolates most often use chemokine receptor CCR5 or CXCR4 as a co-receptor to enter target cells. During early stages of HIV-1 infection, CCR5-tropic viruses are the predominant species. The CXCR4-tropic viruses may emerge late in infection. Recognition of factors influencing this phenotypic switch may give some hints on the antiviral strategies like anti-HIV/AIDS drugs, gene therapy and vaccines.

Methods

To investigate the mechanism that triggers R5 to X4 phenotypic switch, we performed a systematic sensitivity analysis based on a five-dimensional model with time-varying parameters. We studied the sensitivity of each factor to the CCR5-to-CXCR4 tropism switch and acquired some interesting outcomes beyond expectation.

Results

The death rate of free virus (dV), rate that uninfected CD4+ Tcells arise from precursors (s) and proliferate as stimulated by antigens (r), and in vivo viral burst size (N) are four robust factors which are constantly observed to have a strong correlation with the evolution of viral phenotype for most patients longitudinally.

Conclusions

Crucial factors, which are essential to phenotypic switch and disease progression, are almost the same for different patients at different time points, including the production of both virus and CD4+ Tcells and the decay of virion. It is also worth mentioning that although the sequence of factors sorted by the influence varies between patients, the trends of influences engendered by most factors as disease progresses are similar inter-patients.

Keywords

HIV-1 R5-to-X4 switch two-strain model population dynamics sensitivity analysis 

Notes

Acknowledgements

We acknowledge the supports from the National Natural Science Foundation of China (Nos. 11402227, 11621062 and 11432012), the Fundamental Research Funds for the Central Universities of China (No. 2015QNA4034), and the Thousand Young Talents Program of China.

Supplementary material

40484_2017_107_MOESM1_ESM.pdf (2 mb)
A Systematic Analysis of Intrinsic Regulators for HIV-1 R5 to X4 Phenotypic Switch

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Copyright information

© Higher Education Press and Springer-Verlag GmbH 2017

Authors and Affiliations

  1. 1.Department of Engineering MechanicsZhejiang UniversityHangzhouChina
  2. 2.Key Laboratory of Soft Machines and Smart Devices of Zhejiang ProvinceZhejiang UniversityHangzhouChina
  3. 3.Soft Matter Research CenterZhejiang UniversityHangzhouChina

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