title: Virome analysis of antiretroviral-treated HIV patients shows no correlation between T-cell activation and anelloviruses levels.
abstract: BACKGROUND
  Abnormally high levels of T-cell activation can persist in HIV-infected subjects despite effective anti-retroviral therapy (ART) and has been associated with negative health outcomes. The nature of the antigenic drivers or other causes of this residual T-cell activation remain uncertain. Anelloviruses are universally acquired soon after birth, resulting in persistent viremia, and considered part of the commensal human virome. Reduced immunocompetence results in increased anellovirus levels.
  
  
  OBJECTIVE
  To test whether increased levels of anelloviruses or other viruses in plasma are associated with higher levels of persistent T-cell activation during ART.
  
  
  METHODS
  Two amplification methods combined with next generation sequencing were used to detect all viruses and estimate relative anellovirus levels in plasma from 19 adults on effective ART who exhibited a wide range of T-cell activation levels.
  
  
  RESULTS
  Nucleic acids from HBV and HCV were detected in one patient each while pegivirus A (GBV-C) was found in three patients. Anellovirus DNA was detected in all patients with some individuals carrying up to eight different genotypes. Specific anellovirus genotypes or higher level of co-infections were not detected in subjects with higher levels of T-cell activation. No association was detected between relative plasma anellovirus DNA levels and the percentage of activated CD4 or CD8 T cells.
  
  
  CONCLUSIONS
  Human anelloviruses were detected in all HIV suppressed subjects, exhibited 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 viremia or genotypes present indicating that anellovirus antigens are unlikely to be a dominant source of antigens driving chronic T-cell activation.
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
authors.forename: Xutao
authors.initials: X
authors.lastname: Deng
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA; Institute of Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Antonio Charlys
authors.initials: AC
authors.lastname: Da Costa
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bruhn
authors.affiliation: Positive Health Program, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA. Electronic address: delwarte@medicine.ucsf.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Delwart
mesh_terms: D000328:Adult; D049811:Anelloviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D004266:DNA Virus Infections / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents
keywords: Anellovirus; HIV; HLA-DR+CD38+; T-cell activation; Torque teno virus; Virome