Reactivation and mutation of newly discovered WU, KI, and Merkel cell carcinoma polyomaviruses in immunosuppressed individuals.
BACKGROUND
Infection with the human polyomaviruses BK (BKV) and JC (JCV) is almost ubiquitous, asymptomatic, and lifelong. However, reactivation during immunosuppression, associated with mutations in the transcriptional control region (TCR) that up-regulates viral replication, can cause life-threatening disease. In this study, we investigated whether the recently discovered WU and KI polyomaviruses (WUPyV and KIPyV) and Merkel cell polyomavirus (MCPyV) could, like BKV and JCV, persist, mutate, and reactivate in immunodeficient subjects.


METHODS
Autopsy samples of lymphoid tissue from 42 AIDS-immunosuppressed subjects and 55 control samples were screened by polymerase chain reaction for all 5 polyomaviruses. TCR sequences from KIPyV and WUPyV recovered from both immunosuppressed and nonimmunosuppressed subjects were compared.


RESULTS
Combined polyomavirus detection frequencies were much higher for the immunosuppressed group, compared with the nonimmunosuppressed group (35.7% vs. 3.6%), with viral loads in lymphoid tissues ranging from < or = 8.4 x 10(5) to > 1.5 x 10(5) viral genome copies per 10(6) cells. MCPyV was recovered from only 1 HIV-negative study subject. TCR sequences from reactivated WUPyV and KIPyV variants showed a number of point mutations and insertions that were absent in viruses recovered from respiratory tract specimens obtained from nonimmunosuppressed subjects.


CONCLUSIONS
KIPyV and WUPyV show reactivation frequencies comparable to those of BKV and JCV during immunosuppression. TCR changes that potentially lead to transcriptional dysregulation may have pathogenic consequences equivalent in severity to those observed for JCV and BKV.
Sharp
Colin P
CP
Centre for Infectious Diseases, Neuropathology Unit, University of Edinburgh, United Kingdom.
Norja
Päivi
P
Anthony
Iain
I
Bell
Jeanne E
JE
Simmonds
Peter
P
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology; D015266:Carcinoma, Merkel Cell / Q000821:virology; D006801:Humans; D016867:Immunocompromised Host; D008221:Lymphoid Tissue / Q000821:virology; D016133:Polymerase Chain Reaction; D011120:Polyomavirus / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D027601:Polyomavirus Infections / Q000276:immunology / Q000821:virology*; D012137:Respiratory System / Q000821:virology; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology*; D054334:Viral Regulatory and Accessory Proteins / Q000302:isolation & purification; D014775:Virus Activation / Q000276:immunology
D054334:Viral Regulatory and Accessory Proteins