Official websites use. Share sensitive information only on official, secure websites. Background : An overwhelming obstacle to HIV cure is the presence of long-lived viral reservoirs that can reignite viral infection after removal of combination antiretroviral therapy cART.
Yet, our knowledge of the mechanisms of reservoir maintenance and persistence remains incompletely understood. Therefore, in this study, we generated a novel virus model for evaluating individual reactivation events following cART interruption to better understand key aspects of reservoir biology in vivo. Next-generation sequencing was used to evaluate the number of genetic variants in the stock and in plasma before and after treatment.
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Results : In the viral stock, individual barcodes, or clonotypes, were identified. During acute infection, an average of barcodes were identified in each of the 10 animals. Between 87 and distinct clonotypes were detected in plasma at peak rebound viraemia in animals from study 1 and between 4 and 7 clonotypes in animals from study 2. Because the growth rate of each clonotype is equivalent once the virus reaches systemic infection, the measured relative proportions of each clonotype at rebound reflect the time between when each clonotype achieved systemic infection.
The viral growth rate and the relative abundance of each clonotype in plasma during acute recrudescence were used to estimate a reactivation rate of Conclusions : We conclude that identifying rebounding clonotypes may be used as a direct measurement of the latent reservoir that can successfully contribute to rebound viraemia.
Furthermore, the results confirm that the size of the post-cART recrudescence-competent viral reservoir is influenced by the timing of cART initiation and duration of treatment, enabling manipulation of these parameters to establish reservoirs of desired size for specific experimental purposes. HIV-infected cells can undergo clonal expansion, and specific clones may be highly expanded. Mechanisms by which clones emerge and persist over time are uncertain.
