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Campos GMD, Costa TCDM, Silva ASD, Costa LOA, Silveira RM, Valença IN, Carvalho FSD, Júnior LGD, Haddad R, Vieira ACDJ, Mesquita CC, Laurindo PDS, Cunha RG, Alcântara LCJ, Kashima S, Covas DT, Simões BP, Sampaio SC, Elias MC, Giovanetti M, Junqueira DM, Slavov SN. Molecular Profile and Dynamics of Commensal Viruses in Brazilian Patients Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation. Transpl Infect Dis 2025:e70037. [PMID: 40298332 DOI: 10.1111/tid.70037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 03/26/2025] [Accepted: 04/07/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND Commensal viruses are typically well-tolerated by healthy individuals, but their behavior in immunocompromised patients is not fully understood. METHODS This study investigated the prevalence, molecular dynamics, and circulating genotypes of human pegivirus-1 (HPgV-1) and three types of torque teno viruses (TTV-3, -16, and -22) in Brazilian patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Plasma samples from 20 patients were collected at three time points: pretransplantation (D+0), 30 days post-transplantation (D+30), and 100 days post-transplantation (D+100). We conducted longitudinal screening for HPgV-1 and three TTV variants using real-time PCR, comparing cycle threshold values across these intervals. RESULTS The overall HPgV-1 RNA prevalence at all collection points was 45% (n = 9/20), with all infected individuals carrying genotype 2. HPgV-1 infections exhibited stable, closely related strains over time, though virus evolution was highly individualized. The overall prevalence of TTV types was 5% for TTV-3, 30% for TTV-16, and 60% for TTV-22. Notably, all commensal viruses showed a decrease in cycle threshold at D+100, indicating a possible increase in viral load. CONCLUSION These findings underscore the importance of commensal viruses in the context of HSCT and suggest their potential role as biomarkers for immune suppression and transplantation outcomes. Further research is warranted to elucidate their implications.
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Affiliation(s)
- Gabriel Montenegro de Campos
- Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Thalita Cristina de Mello Costa
- Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Anielly Sarana da Silva
- Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Lara Okuyama Afonso Costa
- Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Roberta Maraninchi Silveira
- Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Ian Nunes Valença
- Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Felipe Santos de Carvalho
- Special Unit for Treatment of Infectious Diseases (UETDI), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | - Rodrigo Haddad
- Faculty of Ceilândia, University of Brasília, Brasília Distrito Federal, Brazil
| | - Ana Carolina de Jesus Vieira
- Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Camila Campos Mesquita
- Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Patrícia da Silva Laurindo
- Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | | | - Simone Kashima
- Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Dimas Tadeu Covas
- Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Belinda Pinto Simões
- Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | | | - Marta Giovanetti
- Department of Sciences and Technologies for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, Rome, Italy
- Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Minas Gerais, Minas Gerais, Brazil
| | - Dennis Maletich Junqueira
- Post-graduation Program in Biological Sciences: Toxicologic Biochemistry, Laboratory of Bioinformatics and Viral Evolution (LABEVIR), Federal University of Santa Maria-UFSM, Santa Maria, Rio Grande do Sul, Brazil
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Loy C, Cheng MP, Gonzalez-Bocco IH, Lenz J, Belcher E, Bliss A, Eweis-LaBolle D, Chu T, Ritz J, De Vlaminck I. Cell-free RNA Liquid Biopsy to Monitor Hematopoietic Stem Cell Transplantation. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.05.15.24307448. [PMID: 38798589 PMCID: PMC11118637 DOI: 10.1101/2024.05.15.24307448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
Abstract
Hematopoietic Stem Cell Transplantation (HSCT) is one of the oldest and most successful immunotherapies. Yet, despite long-standing success in the use of HSCT for the treatment of blood cancers and severe immune disorders, monitoring post-transplant complications remains a challenge due to a lack of informative diagnostic tests. Here, we investigate the utility of cell-free RNA (cfRNA) in plasma as a liquid biopsy to monitor allogeneic HSCT recipients during and after treatment. We assayed longitudinal samples from 92 HSCT recipients by cfRNA sequencing and show that cfRNA provides insight into treatment and recovery trajectories, immune dynamics in response to transplantation, infection, and solid-tissue injury associated with Graft-Versus-Host Disease. Collectively, our results provide support for the use of plasma cfRNA profiling to monitor complications of HSCT.
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Affiliation(s)
- Conor Loy
- Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA
- Department of Molecular Biology and Genetics, Cornell University; Ithaca, 14853, USA
| | - Matthew P. Cheng
- Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA
- Division of Infectious Disease, Brigham and Women’s Hospital; Boston, 02215, USA
| | - Isabel H. Gonzalez-Bocco
- Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA
- Division of Infectious Disease, Brigham and Women’s Hospital; Boston, 02215, USA
| | - Joan Lenz
- Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA
| | - Emma Belcher
- Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA
| | - Andrew Bliss
- Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA
| | - Daniel Eweis-LaBolle
- Department of Molecular Biology and Genetics, Cornell University; Ithaca, 14853, USA
| | - Tinyi Chu
- Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA
| | - Jerome Ritz
- Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA
- Department of Medicine, Harvard Medical School, Boston, 02115, USA
| | - Iwijn De Vlaminck
- Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA
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3
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Forqué L, Albert E, Piñana JL, Pérez A, Hernani R, Solano C, Navarro D, Giménez E. Monitoring of plasma Torque teno virus, total Anelloviridae and Human Pegivirus 1 viral load for the prediction of infectious events and acute graft versus host disease in the allogeneic hematopoietic stem cell transplantation setting. J Med Virol 2023; 95:e29107. [PMID: 37721473 DOI: 10.1002/jmv.29107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 09/05/2023] [Accepted: 09/06/2023] [Indexed: 09/19/2023]
Abstract
Anelloviridae and Human Pegivirus 1 (HPgV-1) blood burden have been postulated to behave as surrogate markers for immunosuppression in transplant recipients. Here, we assessed the potential utility plasma Torque teno virus (TTV), total Anelloviridae (TAV), and HPgV-1 load monitoring for the identification of allogeneic hematopoietic stem cell transplantation recipients (allo-HSCT) at increased risk of infectious events or acute graft versus host disease (aGvHD). In this single-center, observational study, plasma TTV DNA, TAV DNA, and HPgV-1 RNA loads were monitored in 75 nonconsecutive allo-HSCT recipients (median age, 54 years). Monitoring was conducted before at baseline or by days +30, +60, +90, +120, and +180 after transplantation. Pneumonia due to different viruses or Pneumocystis jirovecii, BK polyomavirus-associated haemorrhagic cystitis (BKPyV-HC), and Cytomegalovirus DNAemia were the infectious events considered in the current study. Kinetics of plasma TTV, TAV DNA, and HPgV-1 RNA load was comparable, with though and peak levels measured by days +30 and day +90 (+120 for HPgV-1). Forty patients (53%) developed one or more infectious events during the first 180 days after allo-HSCT, whereas 29 patients (39%) had aGvHD (grade II-IV in 18). Neither, TTV, TAV, nor HPgV-1 loads were predictive of overall infection or CMV DNAemia. A TTV DNA load cut-off ≥4.40 log10 (pretransplant) and ≥4.58 log10 (baseline) copies/mL predicted the occurrence of BKPyV-HC (sensitivity ≥89%, negative predictive value, ≥96%). TTV DNA loads ≥3.38 log10 by day +30 anticipated the occurrence of aGvHD (sensitivity, 90%; negative predictive value, 97%). Pretransplant HPgV-1 loads were significantly lower (p = 0.03) in patients who had aGvHD than in those who did not. Monitoring of TTV DNA or HPgV-1 RNA plasma levels either before or early after transplantation may be ancillary to identify allo-HSCT recipients at increased risk of BKPyV-HC or aGvHD.
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Affiliation(s)
- Lorena Forqué
- Microbiology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
| | - Eliseo Albert
- Microbiology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
| | - José L Piñana
- Hematology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
| | - Ariadna Pérez
- Hematology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
| | - Rafael Hernani
- Hematology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
| | - Carlos Solano
- Hematology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
- Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain
| | - David Navarro
- Microbiology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain
| | - Estela Giménez
- Microbiology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
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Zanella MC, Vu DL, Hosszu-Fellous K, Neofytos D, Van Delden C, Turin L, Poncet A, Simonetta F, Masouridi-Levrat S, Chalandon Y, Cordey S, Kaiser L. Longitudinal Detection of Twenty DNA and RNA Viruses in Allogeneic Hematopoietic Stem Cell Transplant Recipients Plasma. Viruses 2023; 15:v15040928. [PMID: 37112908 PMCID: PMC10142697 DOI: 10.3390/v15040928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/29/2023] [Accepted: 04/05/2023] [Indexed: 04/29/2023] Open
Abstract
Metagenomics revealed novel and routinely overlooked viruses, representing sources of unrecognized infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to describe DNA and RNA virus prevalence and kinetics in allo-HSCT recipients' plasma for one year post HSCT. We included 109 adult patients with first allo-HSCT from 1 March 2017 to 31 January 2019 in this observational cohort study. Seventeen DNA and three RNA viral species were screened with qualitative and/or quantitative r(RT)-PCR assays using plasma samples collected at 0, 1, 3, 6, and 12 months post HSCT. TTV infected 97% of patients, followed by HPgV-1 (prevalence: 26-36%). TTV (median 3.29 × 105 copies/mL) and HPgV-1 (median 1.18 × 106 copies/mL) viral loads peaked at month 3. At least one Polyomaviridae virus (BKPyV, JCPyV, MCPyV, HPyV6/7) was detected in >10% of patients. HPyV6 and HPyV7 prevalence reached 27% and 12% at month 3; CMV prevalence reached 27%. HSV, VZV, EBV, HHV-7, HAdV and B19V prevalence remained <5%. HPyV9, TSPyV, HBoV, EV and HPg-V2 were never detected. At month 3, 72% of patients had co-infections. TTV and HPgV-1 infections were highly prevalent. BKPyV, MCPyV and HPyV6/7 were frequently detected relative to classical culprits. Further investigation is needed into associations between these viral infections and immune reconstitution or clinical outcomes.
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Affiliation(s)
- Marie-Céline Zanella
- Division of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland
- Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
| | - Diem-Lan Vu
- Division of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland
- Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland
| | - Krisztina Hosszu-Fellous
- Division of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland
- Geneva Centre for Emerging Viral Diseases, 1211 Geneva, Switzerland
| | - Dionysios Neofytos
- Division of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
| | - Chistian Van Delden
- Division of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
| | - Lara Turin
- Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland
| | - Antoine Poncet
- Center for Clinical Research, Department of Health and Community Medicine, University of Geneva, 1206 Geneva, Switzerland
- Division of Clinical Epidemiology, Department of Health and Community Medicine, University Hospital of Geneva, 1211 Geneva, Switzerland
| | - Federico Simonetta
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
- Division of Hematology, Department of Oncology, Geneva University Hospitals, 1211 Geneva, Switzerland
| | - Stavroula Masouridi-Levrat
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
- Division of Hematology, Department of Oncology, Geneva University Hospitals, 1211 Geneva, Switzerland
| | - Yves Chalandon
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
- Division of Hematology, Department of Oncology, Geneva University Hospitals, 1211 Geneva, Switzerland
| | - Samuel Cordey
- Division of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland
- Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
| | - Laurent Kaiser
- Division of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland
- Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland
- Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland
- Geneva Centre for Emerging Viral Diseases, 1211 Geneva, Switzerland
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Ludowyke N, Phumiphanjarphak W, Apiwattanakul N, Manopwisedjaroen S, Pakakasama S, Sensorn I, Pasomsub E, Chantratita W, Hongeng S, Aiewsakun P, Thitithanyanont A. Target Enrichment Metagenomics Reveals Human Pegivirus-1 in Pediatric Hematopoietic Stem Cell Transplantation Recipients. Viruses 2022; 14:796. [PMID: 35458526 PMCID: PMC9025367 DOI: 10.3390/v14040796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 11/17/2022] Open
Abstract
Human pegivirus-1 (HPgV-1) is a lymphotropic human virus, typically considered nonpathogenic, but its infection can sometimes cause persistent viremia both in immunocompetent and immunosuppressed individuals. In a viral discovery research program in hematopoietic stem cell transplant (HSCT) pediatric patients, HPgV-1 was detected in 3 out of 14 patients (21.4%) using a target enrichment next-generation sequencing method, and the presence of the viruses was confirmed by agent-specific qRT-PCR assays. For the first time in this patient cohort, complete genomes of HPgV-1 were acquired and characterized. Phylogenetic analyses indicated that two patients had HPgV-1 genotype 2 and one had HPgV-1 genotype 3. Intra-host genomic variations were described and discussed. Our results highlight the necessity to screen HSCT patients and blood and stem cell donors to reduce the potential risk of HPgV-1 transmission.
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Affiliation(s)
- Natali Ludowyke
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; (N.L.); (W.P.); (S.M.)
| | - Worakorn Phumiphanjarphak
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; (N.L.); (W.P.); (S.M.)
- Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Nopporn Apiwattanakul
- Department of Pediatrics, Division of Hematology and Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (N.A.); (S.P.); (S.H.)
| | - Suwimon Manopwisedjaroen
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; (N.L.); (W.P.); (S.M.)
| | - Samart Pakakasama
- Department of Pediatrics, Division of Hematology and Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (N.A.); (S.P.); (S.H.)
| | - Insee Sensorn
- Center for Medical Genomics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (I.S.); (W.C.)
| | - Ekawat Pasomsub
- Virology and Molecular Microbiology Unit, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Wasun Chantratita
- Center for Medical Genomics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (I.S.); (W.C.)
| | - Suradej Hongeng
- Department of Pediatrics, Division of Hematology and Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (N.A.); (S.P.); (S.H.)
| | - Pakorn Aiewsakun
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; (N.L.); (W.P.); (S.M.)
- Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Arunee Thitithanyanont
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; (N.L.); (W.P.); (S.M.)
- Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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Samadi M, Salimi V, Haghshenas MR, Miri SM, Mohebbi SR, Ghaemi A. Clinical and molecular aspects of human pegiviruses in the interaction host and infectious agent. Virol J 2022; 19:41. [PMID: 35264187 PMCID: PMC8905790 DOI: 10.1186/s12985-022-01769-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/16/2022] [Indexed: 12/11/2022] Open
Abstract
Background Human pegivirus 1 (HPgV-1) is a Positive-sense single-stranded RNA (+ ssRNA) virus, discovered in 1995 as a Flaviviridae member, and the closest human virus linked to HCV. In comparison to HCV, HPgV-1 seems to be lymphotropic and connected to the viral group that infects T and B lymphocytes. HPgV-1 infection is not persuasively correlated to any known human disease; nevertheless, multiple studies have reported a connection between chronic HPgV-1 infection and improved survival in HPgV-1/HIV co-infected patients with a delayed and favorable impact on HIV infection development. While the process has not been thoroughly clarified, different mechanisms for these observations have been proposed. HPgV-1 is categorized into seven genotypes and various subtypes. Infection with HPgV-1 is relatively common globally. It can be transferred parenterally, sexually, and through vertical ways, and thereby its co-infection with HIV and HCV is common. In most cases, the clearance of HPgV-1 from the body can be achieved by developing E2 antibodies after infection. Main body In this review, we thoroughly discuss the current knowledge and recent advances in understanding distinct epidemiological, molecular, and clinical aspects of HPgV-1. Conclusion Due to the unique characteristics of the HPgV-1, so advanced research on HPgV-1, particularly in light of HIV co-infection and other diseases, should be conducted to explore the essential mechanisms of HIV clearance and other viruses and thereby suggest novel strategies for viral therapy in the future.
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Affiliation(s)
- Mehdi Samadi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Department of Microbiology, Molecular and Cell-Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Vahid Salimi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Haghshenas
- Department of Microbiology, Molecular and Cell-Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Seyed Mohammad Miri
- Department of Virology, Pasteur Institute of Iran, P.O. Box: 1316943551, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ghaemi
- Department of Virology, Pasteur Institute of Iran, P.O. Box: 1316943551, Tehran, Iran.
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Yu Y, Wan Z, Wang JH, Yang X, Zhang C. Review of human pegivirus: Prevalence, transmission, pathogenesis, and clinical implication. Virulence 2022; 13:324-341. [PMID: 35132924 PMCID: PMC8837232 DOI: 10.1080/21505594.2022.2029328] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Human pegivirus (HPgV-1), previously known as GB virus C (GBV-C) or hepatitis G virus (HGV), is a single-stranded positive RNA virus belonging to the genus Pegivirus of the Flaviviridae family. It is transmitted by percutaneous injuries (PIs), contaminated blood and/or blood products, sexual contact, and vertical mother-to-child transmission. It is widely prevalent in general population, especially in high-risk groups. HPgV-1 viremia is typically cleared within the first 1–2 years of infection in most healthy individuals, but may persist for longer periods of time in immunocompromised individuals and/or those co-infected by other viruses. A large body of evidences indicate that HPgV-1 persistent infection has a beneficial clinical effect on many infectious diseases, such as acquired immunodeficiency syndrome (AIDS) and hepatitis C. The beneficial effects seem to be related to a significant reduction of immune activation, and/or the inhabitation of co-infected viruses (e.g. HIV-1). HPgV-1 has a broad cellular tropism for lymphoid and myeloid cells, and preferentially replicates in bone marrow and spleen without cytopathic effect, implying a therapeutic potential. The paper aims to summarize the natural history, prevalence and distribution characteristics, and pathogenesis of HPgV-1, and discuss its association with other human viral diseases, and potential use in therapy as a biovaccine or viral vector.
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Affiliation(s)
- Yaqi Yu
- College of Life Sciences, Henan Normal University, Xinxiang, China.,Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zhenzhou Wan
- Medical Laboratory of Taizhou Fourth People's Hospital, Taizhou, China
| | - Jian-Hua Wang
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Xianguang Yang
- College of Life Sciences, Henan Normal University, Xinxiang, China
| | - Chiyu Zhang
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Mrzljak A, Simunov B, Balen I, Jurekovic Z, Vilibic-Cavlek T. Human pegivirus infection after transplant: Is there an impact? World J Transplant 2022; 12:1-7. [PMID: 35096551 PMCID: PMC8771596 DOI: 10.5500/wjt.v12.i1.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 10/25/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
The microbiome's role in transplantation has received growing interest, but the role of virome remains understudied. Pegiviruses are single-stranded positive-sense RNA viruses, historically associated with liver disease, but their path-ogenicity is controversial. In the transplantation setting, pegivirus infection does not seem to have a negative impact on the outcomes of solid-organ and hematopoietic stem cell transplant recipients. However, the role of pegiviruses as proxies in immunosuppression monitoring brings novelty to the field of virome research in immunocompromised individuals. The possible immunomodulatory effect of pegivirus infections remains to be elucidated in further trials.
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Affiliation(s)
- Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Bojana Simunov
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
| | - Ivan Balen
- Department of Gastroenterology and Endocrinology, General Hospital “Dr. Josip Bencevic”, Slavonski Brod 35000, Croatia
| | - Zeljka Jurekovic
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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9
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Fernández-Ruiz M, Forque L, Albert E, Redondo N, Giménez E, López-Medrano F, González E, Polanco N, Ruiz-Merlo T, Parra P, San Juan R, Andrés A, Aguado JM, Navarro D. Human pegivirus type 1 infection in kidney transplant recipients: Replication kinetics and clinical correlates. Transpl Infect Dis 2021; 24:e13771. [PMID: 34921747 DOI: 10.1111/tid.13771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/23/2021] [Accepted: 11/29/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. METHODS We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. RESULTS HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. CONCLUSION Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.
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Affiliation(s)
- Mario Fernández-Ruiz
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Lorena Forque
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Eliseo Albert
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Natalia Redondo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Estela Giménez
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.,Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Esther González
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Natalia Polanco
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Patricia Parra
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Rafael San Juan
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.,Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Amado Andrés
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.,Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.,Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - David Navarro
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.,Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain
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Shaker EK, Al-Jebouri MM, Al-Mayah QS, Al-Matubsi HY. Phylogenetic analysis of human pegivirus from anti-hepatitis C virus IgG- positive patients. INFECTION GENETICS AND EVOLUTION 2021; 96:105099. [PMID: 34601095 DOI: 10.1016/j.meegid.2021.105099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/20/2021] [Accepted: 09/27/2021] [Indexed: 12/24/2022]
Abstract
Human pegivirus type 1 (HPgV-1) is a non-pathogenic RNA virus in the Flaviviridae family that usually occurs as a co-infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), though some evidence suggests it may play a role in certain cancers. The present study aimed to determine the prevalence of HPgV-1 infection in Iraqi anti-HCV IgG-positive patients, the risk factors associated with this infection, and the genotype of local isolates of this virus. A total of 88 anti-HCV IgG-positive patients participated in this cross-sectional study. Viral RAN was extracted from whole blood samples, and cDNA was produced using reverse transcriptase-polymerase chain reaction (RT-PCR). Two pairs of primers were used in nested PCR to amplify the virus genome's 5'-untranslated region (5'UTR). For direct sequencing, fourteen PCR products from the second round of PCR were chosen at random. A homology search was performed using the basic local alignment search tool (BLAST) program to identify the resultant sequencing. The phylogenetic tree of the local isolates and 31 reference isolates was constructed using MEGA X software to estimate the virus's genetic diversity and relatedness. Out of 88 patients included in this study, 27(30.68%) of patients were found to be positive for HPgV-1 RNA. The nucleotide homology between the 14 local isolates and the reference isolates. was found to be 87-97%. Phylogenetic analysis results in a tree with four main parts, which are distributed as follows: 10 local isolates are genotype 2; 2 are genotype 1; 1 is genotype 5, and 1 is genotype 6. We conclude that when compared to other countries, the infection rate of Iraqi anti-HCV IgG-positive patients with HPgV-1 is relatively high (30.68%). The most common HPgV-1 genotype in Iraq is genotype 2.
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Affiliation(s)
- Ekremah K Shaker
- Medical Laboratory Technique, Al-Rasheed University College, Iraq
| | | | - Qasim S Al-Mayah
- Medical Research Unit, College of Medicine, Al-Nahrain University, Iraq
| | - Hisham Y Al-Matubsi
- Department of Pharmacology and Medical Sciences, University of Petra, Amman, Jordan.
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Human pegivirus 1 infection in lung transplant recipients: Prevalence, clinical relevance and kinetics of viral replication under immunosuppressive therapy. J Clin Virol 2021; 143:104937. [PMID: 34416522 DOI: 10.1016/j.jcv.2021.104937] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 07/22/2021] [Indexed: 01/23/2023]
Abstract
BACKGROUND Human pegivirus 1 (HPgV1) may cause persistent infections in immunocompetent and immunosuppressed individuals. Its clinical relevance, however, has not been determined. Previous studies have described a higher prevalence of HPgV1 infection in organ transplant recipients compared to healthy controls, but its occurrence in lung transplant recipients (LTRs) and its association with immunosuppressive therapy has not been assessed. OBJECTIVES The aim of this study was to evaluate the prevalence and clinical significance of HPgV1 infection in LTRs, and to compare HPgV1 loads and kinetics to Torque Teno Virus (TTV) kinetics, which reflects the level of immunosuppression. STUDY DESIGN From each of 110 LTRs, five consecutive plasma samples were collected within the first year after transplantation and tested for HPgV1 RNA and TTV DNA loads by quantitative PCR. Data were related to demographic data and clinical parameters followed up for 3 years post transplantation. RESULTS HPgV1 prevalence in LTRs was 18,2%. HPgV1 detection was significantly associated with younger age, but not with graft rejections or other microbial infections. The viral replication level remained unaffected by immunosuppressive therapy. This was in contrast to TTV loads which increased after initiation of immunosuppressive therapy, independent of the patients' HPgV1 infection status. CONCLUSIONS In contrast to TTV, HPgV1 kinetics do not reflect the level of immunosuppression after lung transplantation, and there is no correlation between the replication of both persistent viruses in the post transplantation follow up. Thus the individual virus host interactions seem to differ substantially and require further investigation.
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Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients. Clin Microbiol Rev 2020; 33:33/4/e00027-20. [PMID: 32847820 DOI: 10.1128/cmr.00027-20] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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.
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