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Structured Observations Reveal Slow HIV-1 CTL Escape


The cytotoxic T-lymphocyte (CTL) arm of the immune response is thought to play a significant role in the control of HIV-1 infection. Mutations within the HIV-1 genome allow the virus to escape recognition by CTLs and so evade the immune response. These escape mutations have been well documented but observed waiting times to escape within an individual have ranged from days to years. Many studies describing CTL escape have taken a detailed look at a few patients. Our analysis is based on a cohort of 125 clinical trial participants with immunologic and viral sequence data taken at regular longitudinal time points within the first few years of infection. Results suggested that the majority of CTL-related mutations present early in infection had been transmitted in the infecting viral strain as opposed to arising in the new host due to selection pressure imposed by CTLs. Whilst the prevalence of CTL escape mutations in the dataset was high, the incidence of new escape was relatively low; around one third of patients did not drive an escape within the first two years. Patients possessing a ‘protective’ HLA genotype had a significantly shorter waiting time to first escape than those without.


Vyšlo v časopise: Structured Observations Reveal Slow HIV-1 CTL Escape. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004914
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004914

Souhrn

The cytotoxic T-lymphocyte (CTL) arm of the immune response is thought to play a significant role in the control of HIV-1 infection. Mutations within the HIV-1 genome allow the virus to escape recognition by CTLs and so evade the immune response. These escape mutations have been well documented but observed waiting times to escape within an individual have ranged from days to years. Many studies describing CTL escape have taken a detailed look at a few patients. Our analysis is based on a cohort of 125 clinical trial participants with immunologic and viral sequence data taken at regular longitudinal time points within the first few years of infection. Results suggested that the majority of CTL-related mutations present early in infection had been transmitted in the infecting viral strain as opposed to arising in the new host due to selection pressure imposed by CTLs. Whilst the prevalence of CTL escape mutations in the dataset was high, the incidence of new escape was relatively low; around one third of patients did not drive an escape within the first two years. Patients possessing a ‘protective’ HLA genotype had a significantly shorter waiting time to first escape than those without.


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