Metagenomics is greatly improving our ability to discover new viruses, as well as their possible associations with disease. However, metagenomics has also changed our understanding of viruses in general. The vast expansion of currently known viral diversity has revealed a large fraction of non-pathogenic viruses, and offers a new perspective in which viruses function as important components of many ecosystems. In this vein, studies of the human blood virome are often motivated by the search for new viral diseases, especially those associated with blood transfusions. However, these studies have revealed the common presence of apparently non-pathogenic viruses in blood, particularly human anelloviruses and, to a lower extent, human pegiviruses (HPgV). To shed light on the diversity of the human blood virome, we subjected pooled plasma samples from 587 healthy donors in Spain to a viral enrichment protocol, followed by massive parallel sequencing. This showed that anelloviruses were clearly the major component of the blood virome and showed remarkable diversity. In total, we assembled 332 complete or near-complete anellovirus genomes, 50 of which could be considered new species. HPgV was much less frequent, but we, nevertheless, recovered 17 different isolates that we subsequently used for characterizing the diversity of this virus. In-depth investigation of the human blood virome should help to elucidate the ecology of these viruses, and to unveil potentially associated diseases.

Anelloviruses are the most common human infectious viruses and are considered essentially harmless. Compared to other human viruses, they are characterized by enormous diversity, and recombination is suggested to play an important role in their diversification and evolution.

High-dose chemotherapy supported by autologous stem cell transplant (ASCT) remains the treatment of choice for patients with lymphoma failing first-line chemotherapy. Recent evidence suggests a relationship between the genetic variations in genes involved in DNA repair and the outcome of patients with a number of malignancies. In this work, we retrospectively evaluated the influence of an XRCC1 polymorphism (rs25487) on the treatment results in a series of 73 patients with lymphoma subjected to ASCT. The factors correlated to overall survival were the disease status at transplant and XRCC1 genotype. Carriers of a mutant A allele had a two-fold higher risk of death than those with the wild-type genotype. In addition, patients harboring one or two copies of the A allele (GA/AA) were 4.5-fold more likely to develop therapy-related acute myeloid (t-AML). Thus, the cumulative probability of t-AML at 10 years was 37 ± 13% in patients with the mutant A allele as compared to 8.5 ± 6% in the remaining cases (p = 0.04). Our findings suggest that genetic variation in the DNA repair gene XRCC1 may play a role in the results of transplant in patients with lymphoma.