Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients

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Abstract

Human Polyomavirus (HPyV) infections are common, ranging from 60% to 100%. In kidney transplant (KTx) recipients, HPyVs have been associated with allograft nephropathy, progressive multifocal leukoencephalopathy, and skin cancer. Whether such complications are caused by viral reactivation or primary infection transmitted by the donor remains debated. This study aimed to investigate the replication pattern and genomic characterization of BK Polyomavirus (BKPyV), JC Polyomavirus (JCPyV), and Merkel Cell Polyomavirus (MCPyV) infections in KTx. Urine samples from 57 KTx donor/recipient pairs were collected immediately before organ retrieval/transplant and periodically up to post-operative day 540. Specimens were tested for the presence of BKPyV, JCPyV, and MCPyV genome by virus-specific Real-Time PCR and molecularly characterized. HPyVs genome was detected in 49.1% of donors and 77.2% of recipients. Sequences analysis revealed the archetypal strain for JCPyV, TU and Dunlop strains for BKPyV, and IIa-2 strain for MCPyV. VP1 genotyping showed a high frequency for JCPyV genotype 1 and BKPyV genotype I. Our experience demonstrates that after KTx, HPyVs genome remains stable over time with no emergence of quasi-species. HPyVs strains isolated in donor/recipient pairs are mostly identical, suggesting that viruses detected in the recipient may be transmitted by the allograft.

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Most cited references 67

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Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.

R Wolfe, V. B. Ashby, E Milford … (1999)

The extent to which renal allotransplantation - as compared with long-term dialysis - improves survival among patients with end-stage renal disease is controversial, because those selected for transplantation may have a lower base-line risk of death. In an attempt to distinguish the effects of patient selection from those of transplantation itself, we conducted a longitudinal study of mortality in 228,552 patients who were receiving long-term dialysis for end-stage renal disease. Of these patients, 46,164 were placed on a waiting list for transplantation, 23,275 of whom received a first cadaveric transplant between 1991 and 1997. The relative risk of death and survival were assessed with time-dependent nonproportional-hazards analysis, with adjustment for age, race, sex, cause of end-stage renal disease, geographic region, time from first treatment for end-stage renal disease to placement on the waiting list, and year of initial placement on the list. Among the various subgroups, the standardized mortality ratio for the patients on dialysis who were awaiting transplantation (annual death rate, 6.3 per 100 patient-years) was 38 to 58 percent lower than that for all patients on dialysis (annual death rate, 16.1 per 100 patient-years). The relative risk of death during the first 2 weeks after transplantation was 2.8 times as high as that for patients on dialysis who had equal lengths of follow-up since placement on the waiting list, but at 18 months the risk was much lower (relative risk, 0.32; 95 percent confidence interval, 0.30 to 0.35; P<0.001). The likelihood of survival became equal in the two groups within 5 to 673 days after transplantation in all the subgroups of patients we examined. The long-term mortality rate was 48 to 82 percent lower among transplant recipients (annual death rate, 3.8 per 100 patient-years) than patients on the waiting list, with relatively larger benefits among patients who were 20 to 39 years old, white patients, and younger patients with diabetes. Among patients with end-stage renal disease, healthier patients are placed on the waiting list for transplantation, and long-term survival is better among those on the waiting list who eventually undergo transplantation.

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Infection in Organ Transplantation.

Jay A Fishman (2017)

The prevention, diagnosis and management of infectious disease in transplantation are major contributors to improved outcomes in organ transplantation. The risk of serious infections in organ recipients is determined largely by the interaction between the patient's epidemiological exposures and net state of immune suppression. In organ recipients, there is a significant incidence of drug toxicity and a propensity for drug interactions with immunosuppressive agents used to maintain graft function. Thus, every effort must be made to establish specific microbiologic diagnoses to optimize therapy. A timeline can be created to develop a differential diagnosis of infection in transplantation based on common patterns of infectious exposures, immunosuppressive management, and antimicrobial prophylaxis. Application of quantitative molecular microbial assays and advanced antimicrobial therapies has advanced care. Pathogen-specific immunity, genetic polymorphisms in immune responses, and the dynamic interactions between the microbiome and the risk for infections are beginning to be explored. The role of infection in the stimulation of alloimmune responses awaits further definition. Major hurdles include shifting world-wide epidemiology of infection, increasing antimicrobial resistance, suboptimal screening assays for microbiologic screening of organ donors, and virus-associated malignancies. Transplant infectious disease remains a key to the clinical and scientific investigation of organ transplantation. This article is protected by copyright. All rights reserved.

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Discovery and epidemiology of the human polyomaviruses BK virus (BKV) and JC virus (JCV).

Wendy Knowles (2006)

Although discovered over thirty years ago, many aspects of the epidemiology of BKV and JCV in the general population, such as the source of infectious virus and the mode of transmission, are still unknown. Primary infection with both BKV and JCV is usually asymptomatic, and so age seroprevalence studies have been used to indicate infection. BKV commonly infects young children in all parts of the world, with the exception of a few very isolated communities, adult seroprevalence rates of 65-90% being reached by the age of ten years. In contrast, the pattern of JCV infection appears to vary between populations; in some anti-JCV antibody is acquired early as for BKV, but in others anti-JCV antibody prevalence continues to rise throughout life. This indicates that the two viruses are probably transmitted independently and by different routes. Whilst BKV DNA is found infrequently in the urine of healthy adults, JCV viruria occurs universally, increasing with age, with adult prevalence rates often between 20% and 60%. Four antigenic subtypes have been described for BKV and eight genotypes are currently recognized for JCV. The latter have been used to trace population movements and to reconstruct the population history in various communities.

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Journal

Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 09 November 2020

Publication date Collection: November 2020

Volume: 12

Issue: 11

Electronic Location Identifier: 1280

Affiliations

[1 ]Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milano, Italy; dolci@ 123456unimi.it (M.D.); rosalia.ticozzi@ 123456unimi.it (R.T.); pasquale.ferrante@ 123456unimi.it (P.F.); serena.delbue@ 123456unimi.it (S.D.)

[2 ]Department of Clinical Sciences and Community Health, University of Milano, 20122 Milano, Italy; evaldofavi@ 123456gmail.com (E.F.); mariano.ferraresso@ 123456unimi.it (M.F.)

[3 ]Kidney Transplantation, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy; caterina.colico@ 123456policlinico.mi.it

[4 ]Service of Legal Medicine, San Siro Clinical Institute, 20148 Milano, Italy; basiletraumaforense@ 123456gmail.com

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[* ]Correspondence: lucia.signorini@ 123456unimi.it ; Tel.: +39-025-031-5084

Author information

Lucia Signorini https://orcid.org/0000-0002-6691-736X

Maria Dolci https://orcid.org/0000-0002-1868-1444

Evaldo Favi https://orcid.org/0000-0001-6465-428X

Mariano Ferraresso https://orcid.org/0000-0003-3410-9090

Serena Delbue https://orcid.org/0000-0002-3199-9369

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Publisher ID: viruses-12-01280

DOI: 10.3390/v12111280

PMC ID: 7696855

PubMed ID: 33182443

SO-VID: b1c2e376-86c1-4bf0-b231-8831b16ce278

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients

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Wiley: Novel Coronavirus COVID-19

Most cited references 67

Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.

Infection in Organ Transplantation.

Discovery and epidemiology of the human polyomaviruses BK virus (BKV) and JC virus (JCV).

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