SRA

Background: Abnormally high levels of T-cell activation can persist in HIV-infected patients despite effective anti-retroviral therapy (ARV) and has been associated with negative health outcomes. The antigenic drivers or other causes of this residual T cell activation remain unknown. Anelloviruses are acquired soon after birth resulting in universal chronic viremia in humans and are considered part of the commensal human virome. Reduced immune-competency results in increased anellovirus viremia levels.Objective: To test whether increased anellovirus viremia levels are associated with higher levels of persistent T cell activation in ARV suppressed patients.Design: Measure anellovirus viremia in 19 successfully ARV-treated patients showing a wide range of T cell activation levels.Methods: We compared the levels of anelloviruses in plasma of patients using two different metagenomics approach. Rolling circle amplification (RCA) or random RT-PCR amplification (RA) combined with next generation sequencing was used to compare yields of anellovirus sequence reads. Viral sequence reads were also used for phylogenetic analysis of the highly variable anelloviruses.Results: RCA and RA both amplified diverse anelloviruses from plasmas. The relative anellovirus concentrations obtained by both methods were correlated. No association was detected between relative anellovirus levels in plasma and the percentage of activated CD4 or CD8 T cells (HLA-DR+ CD38+ CD3+). A wide diversity of anelloviruses belonging to all major clades of human anelloviruses were detected. No specific clades or higher level of co-infections were detected in patients with either low or high levels of T-cell activation.Conclusions: Human anelloviruses were detected in all HIV suppressed patients, showed a wide range of viremia levels, and were genetically highly diverse. The level of persistent T-cell activation was not correlated with the level of anellovirus viremia indicating that anellovirus antigens are unlikely to be a dominant source of antigens driving chronic T-cell activation.