Metagenomic Next-Generation Sequencing Reveals Individual Composition and Dynamics of Anelloviruses during Autologous Stem Cell Transplant Recipient Management.

Antonin Bal,Florence Morfin,Jérémie Becker,Gilles Salles,François Mallet,Clémentine Sarkozy,Sophie Trouillet-Assant,Guy Oriol,Karen Brengel-Pesce,Pierre Sesques,Valérie Cheynet,Laurence Josset,Bruno Lina,Alexandre Pachot,Fréderic Reynier,Gaëlle Vilchez

doi:10.3390/v10110633

Abstract

Over recent years, there has been increasing interest in the use of the anelloviruses, the major component of the human virome, for the prediction of post-transplant complications such as severe infections. Due to an important diversity, the comprehensive characterization of this viral family over time has been poorly studied. To overcome this challenge, we used a metagenomic next-generation sequencing (mNGS) approach with the aim of determining the individual anellovirus profile of autologous stem cell transplant (ASCT) patients. We conducted a prospective pilot study on a homogeneous patient cohort regarding the chemotherapy regimens that included 10 ASCT recipients. A validated viral mNGS workflow was used on 108 plasma samples collected at 11 time points from diagnosis to 90 days post-transplantation. A complex interindividual variability in terms of abundance and composition was noticed. In particular, a strong sex effect was found and confirmed using quantitative PCR targeting torque teno virus, the most abundant anellovirus. Interestingly, an important turnover in the anellovirus composition was observed during the course of the disease revealing a strong intra-individual variability. Although more studies are needed to better understand anellovirus dynamics, these findings are of prime importance for their future use as biomarkers of immune competence.

Highlights

Autologous stem cell transplant (ASCT) is the cornerstone of treatment for certain hematological malignancies such as multiple myeloma (MM) or lymphoma
Using metagenomic next-generation sequencing (mNGS), we describe the individual anellovirus profile during the clinical course of 10 MM patients undergoing autologous stem cell transplant (ASCT)
torque teno virus (TTV) represented the most anellovirus detected in the present study, a high rate of coinfections involving torque teno mini virus (TTMV) and/or torque teno midi virus (TTMDV) was found, as previously reported, notably in hematological patients [9]

Summary

Introduction

Autologous stem cell transplant (ASCT) is the cornerstone of treatment for certain hematological malignancies such as multiple myeloma (MM) or lymphoma. The blood viral load monitoring of the torque teno virus (TTV), a virus belonging to the Anelloviridae family, is increasingly proposed in this setting as illustrated by their use for the risk prediction of graft rejection and bacterial infections in solid organ transplant patients [2,3,4]. The current focus on TTV using targeted polymerase chain reaction (PCR) does not reflect the very high genetic diversity of this viral family. As it is an assumption-free technique, viral metagenomics next-generation sequencing (mNGS) is adapted to fully explore anellovirus diversity, and to the detection of novel species [7]. While coinfections with multiple anelloviruses are highly frequent in populations with hematological diseases [9], their detailed composition and dynamics during the clinical course of the disease are still poorly described

Methods

Results

Conclusion