The plasma viral communities associate with clinical profiles in a large-scale haematological patients cohort.

BACKGROUND: Haematological patients exhibit immune system abnormalities that make them susceptible to viral infections. Understanding the relationship between the virome in the blood plasma of haematological patients and their clinical characteristic is crucial for disease management. We aimed to explore the presence of viral pathogens and identify close associations between viral infections and various clinical features. RESULTS: A total of 21 DNA viruses and 6 RNA viruses from 12 virus families were identified from 1383 patients. Patients with haematological diseases exhibited significantly higher diversity, prevalence, and co-detection rates of viral pathogens. During fever episodes, pathogen detection was notably higher, with Epstein-Barr virus (EBV) and Mucorales infections being the most probable culprits for fever symptoms in non-haematological patients. The detection rate of torque teno virus (TTV) significantly increases in haematological patients after transplantation and during primary lung infections. Additionally, TTV-positive patients demonstrate significantly higher absolute neutrophil counts, while C-reactive protein and procalcitonin levels are notably lower. Furthermore, TTV, cytomegalovirus, and parvovirus B19 (B19V) were found to be more prevalent in non-neutropenic patients, while non-viral pathogenic infections, such as Gram-negative bacteria and Mucorales, were more common in neutropenic patients. Pegivirus C (HPgV-C) infection often occurred post-transplantation, regardless of neutropenia. Additionally, some viruses such as TTV, B19V, EBV, and HPgV-C showed preferences for age and seasonal infections. CONCLUSIONS: Analysis of the plasma virome revealed the susceptibility of haematological patients to plasma viral infections at specific disease stages, along with the occurrence of mixed infections with non-viral pathogens. Close associations were observed between the plasma virome and various clinical characteristics, as well as clinical detection parameters. Understanding plasma virome aids in auxiliary clinical diagnosis and treatment, enabling early prevention to reduce infection rates in patients and improve their quality of life. Video Abstract.

Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Plasma Virome Reveals Blooms and Transmission of Anellovirus in Intravenous Drug Users with HIV-1, HCV, and/or HBV Infections.

Intravenous drug users (IDUs) are a high-risk group for HIV-1, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, which are the leading causes of death in IDUs. However, the plasma virome of IDUs and how it is influenced by above viral infections remain unclear. Using viral metagenomics, we determined the plasma virome of IDUs and its association with HIV-1, HCV, and/or HBV infections. Compared with healthy individuals, IDUs especially those with major viral infections had higher viral abundance and diversity. Anelloviridae dominated plasma virome. Coinfections of multiple anelloviruses were common, and anelloviruses from the same genus tended to coexist together. In this study, 4,487 anellovirus ORF1 sequences were identified, including 1,620 (36.1%) with less than 69% identity to any known sequences, which tripled the current number. Compared with healthy controls (HC), more anellovirus sequences were observed in neg-IDUs, and HIV-1, HCV, and/or HBV infections further expanded the sequence number in IDUs, which was characterized by the emergence of novel divergent taxons and blooms of resident anelloviruses. Pegivirus was mainly identified in infected IDUs. Five main pegivirus transmission clusters (TCs) were identified by phylogenetic analysis, suggesting a transmission link. Similar anellovirus profiles were observed in IDUs within the same TC, suggesting transmission of anellome among IDUs. Our data suggested that IDUs suffered higher plasma viral burden especially anelloviruses, which was associated with HIV-1, HCV, and/or HBV infections. Blooms in abundance and unprecedented diversity of anellovirus highlighted active evolution and replication of this virus in blood circulation, and an uncharacterized role it may engage with the host. IMPORTANCE Virome is associated with immune status and determines or influences disease progression through both pathogenic and resident viruses. Increased viral burden in IDUs especially those with major viral infections indicated the suboptimal immune status and high infection risks of these population. Blooms in abundance and unprecedented diversity of anellovirus highlighted its active evolution and replication in the blood circulation, and sensitive response to other viral infections. In addition, transmission cluster analysis revealed the transmission link of pegivirus among IDUs, and the individuals with transmission links shared similar anellome profiles. In-depth monitoring of the plasma virome in high-risk populations is not only needed for surveillance for emerging viruses and transmission networks of major and neglected bloodborne viruses, but also important for a better understanding of commensal viruses and their role it may engage with immune system.

HIV-1 Infection Alters the Viral Composition of Plasma in Men Who Have Sex with Men.

Altered gut virome and expanded abundance of certain viruses were found in HIV-1-infected individuals. It remains largely unknown how plasma virus composition changes during HIV-1 infection and antiretroviral therapy (ART). We performed viral metagenomic analysis on viral particles enriched from human plasma from 101 men who have sex with men (MSM) with or without HIV-1 infection and whether or not on ART and compared the differences in the plasma virome. An increased plasma viral abundance of main eukaryotic viruses was observed during HIV-1 infection in MSM, especially in AIDS patients (CD4+ T cell counts of <200). Anellovirus, pegivirus and hepatitis B virus (HBV) were the most abundant blood-borne viruses detected among MSM and HIV-1-infected individuals, and anellovirus and pegivirus were closely related to HIV-1 infection. High diversity of anelloviruses was found mostly in HIV-1-infected MSM, and their abundance was positively correlated with the HIV-1 viral load, but negatively correlated with both CD4+ T cell counts and CD4+/CD8+ ratio; in contrast, the abundance of pegivirus showed opposite correlations. ART usage could restore the plasma virome toward that of HIV-1-negative individuals. These data showed an expansion in abundance of certain viruses during HIV-1 infection, indicating the higher risk of shedding some blood-borne viruses in these individuals. These investigations indicate that both anellovirus and pegivirus may play certain roles in HIV disease progression.IMPORTANCE Though an increasing number of studies have indicated the existence of an interaction between the virome and human health or disease, the specific role of these plasma viral components remains largely unsolved. We provide evidence here that an altered plasma virome profile is associated with different immune status of HIV-1 infection. Specific resident viruses, such as anellovirus and pegivirus, may directly or indirectly participate in the disease progression of HIV-1 infection. These results can help to determine their clinical relevance and design potential therapies.

Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History.

We analyze whole-genome sequencing data from 141,431 Chinese women generated for non-invasive prenatal testing (NIPT). We use these data to characterize the population genetic structure and to investigate genetic associations with maternal and infectious traits. We show that the present day distribution of alleles is a function of both ancient migration and very recent population movements. We reveal novel phenotype-genotype associations, including several replicated associations with height and BMI, an association between maternal age and EMB, and between twin pregnancy and NRG1. Finally, we identify a unique pattern of circulating viral DNA in plasma with high prevalence of hepatitis B and other clinically relevant maternal infections. A GWAS for viral infections identifies an exceptionally strong association between integrated herpesvirus 6 and MOV10L1, which affects piwi-interacting RNA (piRNA) processing and PIWI protein function. These findings demonstrate the great value and potential of accumulating NIPT data for worldwide medical and genetic analyses.