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Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution.
- Source :
-
Cell host & microbe [Cell Host Microbe] 2018 May 09; Vol. 23 (5), pp. 628-635.e7. - Publication Year :
- 2018
-
Abstract
- BK polyomavirus (BKV) frequently causes nephropathy (BKVN) in kidney transplant recipients (KTRs). BKV has also been implicated in the etiology of bladder and kidney cancers. We characterized BKV variants from two KTRs who developed BKVN followed by renal carcinoma. Both patients showed a swarm of BKV sequence variants encoding non-silent mutations in surface loops of the viral major capsid protein. The temporal appearance and disappearance of these mutations highlights the intra-patient evolution of BKV. Some of the observed mutations conferred resistance to antibody-mediated neutralization. The mutations also modified the spectrum of receptor glycans engaged by BKV during host cell entry. Intriguingly, all observed mutations were consistent with DNA damage caused by antiviral APOBEC3 cytosine deaminases. Moreover, APOBEC3 expression was evident upon immunohistochemical analysis of renal biopsies from KTRs. These results provide a snapshot of in-host BKV evolution and suggest that APOBEC3 may drive BKV mutagenesis in vivo.<br /> (Published by Elsevier Inc.)
- Subjects :
- APOBEC Deaminases
Adult
Amino Acid Substitution
Animals
Antibodies, Neutralizing
Antibodies, Viral
BK Virus immunology
Capsid Proteins genetics
Cell Line
Chromosome Mapping
Cytidine Deaminase
DNA Damage
DNA, Viral analysis
DNA, Viral genetics
Female
HEK293 Cells
Humans
Italy
Kidney Diseases pathology
Kidney Diseases virology
Male
Middle Aged
Mutation
Polyomavirus Infections blood
Polyomavirus Infections immunology
Polyomavirus Infections pathology
Tumor Virus Infections blood
Tumor Virus Infections immunology
Tumor Virus Infections pathology
BK Virus genetics
Cytosine Deaminase physiology
Kidney Transplantation
Polyomavirus Infections virology
Tumor Virus Infections virology
Subjects
Details
- Language :
- English
- ISSN :
- 1934-6069
- Volume :
- 23
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell host & microbe
- Publication Type :
- Academic Journal
- Accession number :
- 29746834
- Full Text :
- https://doi.org/10.1016/j.chom.2018.04.005