Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients

Abstract

Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients. The identification of novel viral species and variants by metagenomic next-generation sequencing has opened up a new field of investigation and new paradigms. Thus, there is a need to thoroughly describe the state of knowledge in this field with a review of all viral infections that should be scrutinized in high-risk populations. Here, we review the eukaryotic DNA and RNA viruses identified in blood, plasma, or serum samples of pediatric and adult SOT/HSCT recipients and the prevalence of their detection, with a particular focus on recently identified viruses and those for which their potential association with disease remains to be investigated, such as members of the Polyomaviridae, Anelloviridae, Flaviviridae, and Astroviridae families. Current knowledge of the clinical significance of these viral infections with associated viremia among transplant recipients is also discussed. To ensure a comprehensive description in these two populations, individuals described as healthy (mostly blood donors) are considered for comparative purposes. The list of viruses that should be on the clinicians' radar is certainly incomplete and will expand, but the challenge is to identify those of possible clinical significance.

Keywords: blood; blood donors; bone marrow transplantation; diagnostics; solid organ transplantation; transplantation; virus.

FIG 1

Schematic representation of the prevalence of the detection of each viral species considered in this review, in whole-blood, plasma, or serum samples of pediatric and adult SOT recipients, HSCT recipients, and nontransplanted individuals. The prevalence rates of the detection of each viral species for each population screened are classified into five categories according to the mean prevalence rates reported in the publications reviewed and are reported on the ordinate axis. The sizes of the dots represent the degrees of evidence of association of viral infections with diseases, according to the publications reviewed. Histograms represent the total number of screened patients reported in the publications reviewed. Symbols: †, according to data discussed in this review, TTV has not been reported as associated with diseases despite being suggested as a potential predictor for clinical outcomes after transplantation; ‡, the novel HAstV prevalence represented here might be overestimated, considering the screening strategies in some of the studies reviewed, in which the screening of blood samples was performed only in patients with other types of clinical samples positive for novel HAstV. Abbreviations: SOT, solid organ transplant; HSCT, hematopoietic stem cell transplant; NTI, nontransplanted individuals; HHV-6, human herpesvirus 6; HHV-7, human herpesvirus 7; JCPyV, JC polyomavirus; BKPyV, BK polyomavirus; KIPyV, Karolinska Institute polyomavirus; WUPyV, Washington University polyomavirus; MCPyV, Merkel cell polyomavirus; HPyV6, human polyomavirus 6; HPyV7, human polyomavirus 7; TSPyV, trichodysplasia spinulosa-associated polyomavirus; HPyV9, human polyomavirus 9; MWPyV, Malawi polyomavirus; STLPyV, Saint Louis polyomavirus; HPyV12, human polyomavirus 12; HPyV13, human polyomavirus 13; LIPyV, Lyon IARC polyomavirus; HAdV, human adenovirus; B19V, parvovirus B19; PARV4, human parvovirus 4; HBoV, human bocavirus; TTV, torque teno virus; GyV, gyrovirus; CyCV, cyclovirus; gemy., gemycircularvirus; HPgV-1, human pegivirus-1; HPgV-2, human pegivirus-2; n. HAstV, novel human astrovirus.