Dynamics Modeling And Systematic Analysis For HIV-1 R5-to-X4 Phenotypic Switch

AIDS is an infectious disease and is becoming more and more epidemic in recent years.Scientists have made numerous efforts on the pathogenesis,clinical treatment and prevention of AIDS.However,up till now,this disease remains incurable.Many mechanisms of the evolution of HIV have not been understood,especially for the phenomenon that strains of virus using CXCR4 chemokine receptor(X4 viruses)emerge in late infection in about 50%of patients.Although many hypotheses have been raised,the reason for this phenotypic switch is still uncertain.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.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.The results suggested 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+ T cells and the decay of viruses.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.Recognition of these may give some hints on the antiviral strategies like anti-HIV/AIDS drugs,gene therapy and vaccines.