Dynamic Correlation between Intrahost HIV-1 Quasispecies Evolution and Disease Progression

Abstract

Quantifying the dynamics of intrahost HIV-1 sequence evolution is one means of uncovering information about the interaction between HIV-1 and the host immune system. In the chronic phase of infection, common dynamics of sequence divergence and diversity have been reported. We developed an HIV-1 sequence evolution model that simulated the effects of mutation and fitness of sequence variants. The amount of evolution was described by the distance from the founder strain, and fitness was described by the number of offspring a parent sequence produces. Analysis of the model suggested that the previously observed saturation of divergence and decrease of diversity in later stages of infection can be explained by a decrease in the proportion of offspring that are mutants as the distance from the founder strain increases rather than due to an increase of viral fitness. The prediction of the model was examined by performing phylogenetic analysis to estimate the change in the rate of evolution during infection. In agreement with our modeling, in 13 out of 15 patients (followed for 3–12 years) we found that the rate of intrahost HIV-1 evolution was not constant but rather slowed down at a rate correlated with the rate of CD4+ T-cell decline. The correlation between the dynamics of the evolutionary rate and the rate of CD4+ T-cell decline, coupled with our HIV-1 sequence evolution model, explains previously conflicting observations of the relationships between the rate of HIV-1 quasispecies evolution and disease progression.

Deformed wing virus and drone mating flights in the honey bee (Apis mellifera): implications for sexual transmission of a major honey bee virus

“…If this threshold is high, then the titres in the drones also become important and by inference, so does the Varroa infestation status of the drone donor colonies. These different perspectives of the importance of virus titre on the probability of transmission highlight the effect antiviral or anti-Varroa treatments can have on the epidemiology and evolution of a virus (Brunetto et al 2009;Lee et al 2008). The high endophallus DWV infection rate itself suggests that venereal transmission is a major transmission route for DWV Yue et al 2006;, which may in part explain the wide distribution of DWV in Europe.…”

HIV-2 Genetic Evolution in Patients with Advanced Disease Is Faster than That in Matched HIV-1 Patients

“…The correlation between disease progression and viral evolution has been investigated in detail for HIV-1 (10,19,25,32,35) but to a lesser extent for HIV-2 (20,22). MacNeil et al reported a low evolutionary rate of HIV-2 in chronic infections (22), and Lemey et al reported that the rate of synonymous substitutions was lower for HIV-2 than for HIV-1 in chronic infections (20).…”

Differential Expression of Rac-1, Cxcr4 and CCR5 on CD4 T-Cells at Different Stages of HIV-1 Disease Relate To Its Progression in Therapy Naive Individuals

“…It has earlier been revealed that CCR5 and CXCR4, the major co-receptors critical for viral entry into the host cells, are differentially expressed on CD4+ T-cells, and their relative expression is closely associated with disease pathogenesis [18][19][20][21][22][23][24]. We studied their expression on different subsets of T-cells including T-regulatory cells and evaluated their role in changing the frequency of these cells with disease progression.…”