Reactivation and Mutation of Newly Discovered WU, KI, and Merkel Cell Carcinoma Polyomaviruses in Immunosuppressed Individuals
Journal of Infectious Diseases
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,
... V, 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 р8.4 ϫ 10 5 to Ͼ1.5 ϫ 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. Members of the Polyomaviridae are small, circular, double-stranded DNA viruses. The 2 human polyomaviruses BK (BKV) and JC (JCV) were discovered in 1971; BKV was recovered from the urine of a renal allograft recipient  and JCV from the brain of a patient with progressive multifocal leukoencephalopathy (PML) . Subsequent serological surveys have shown that both viruses are acquired during childhood, probably by the respiratory route, and generally reach worldwide seroprevalence rates in adults of ϳ75%-80% [3-6].