WU and KI Polyomaviruses in Respiratory Samples from Allogeneic Hematopoietic Cell Transplant Recipients

Jane Kuypers¹

, Angela P. Campbell¹, Katherine A. Guthrie, Nancy L. Wright, Janet A. Englund, Lawrence Corey, and Michael Boeckh

Author affiliations: University of Washington, Seattle, Washington, USA (J. Kuypers, A.P. Campbell, N.L. Wright, J.A. Englund, L. Corey, M. Boeckh); Fred Hutchinson Cancer Research Center, Seattle (J. Kuypers, A.P. Campbell, K.A. Guthrie, J.A. Englund, L. Corey, M. Boeckh); and Seattle Children’s Hospital, Seattle (A.P. Campbell, J.A. Englund)

Abstract

Data are limited regarding 2 new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), in immunocompromised patients. We used real-time PCR to test for these and 12 respiratory viruses in 2,732 nasal wash samples collected during the first year after allogeneic hematopoietic cell transplantation from 222 patients. Specimens were collected weekly until day 100; then at least every 3 months. One year after hematopoietic cell transplantation, the cumulative incidence estimate was 26% for KIPyV and 8% for WUPyV. Age <20 2="2" 4.6="4.6" a="a" acute="acute" and="and" associated="associated" associations="associations" cytomegalovirus="cytomegalovirus" death.="death." detection="detection" disease="disease" graft="graft" hazard="hazard" hospitalization="hospitalization" host="host" in="in" kipyv="kipyv" lymphopenia="lymphopenia" month.="month." nbsp="nbsp" neutropenia="neutropenia" no="no" of="of" or="or" past="past" polyomavirus="polyomavirus" predicted="predicted" previous="previous" production="production" ratio="ratio" reactivation="reactivation" respiratory="respiratory" sputum="sputum" the="the" there="there" versus="versus" virus="virus" week="week" weeks="weeks" were="were" wheezing="wheezing" with="with" wupyv="wupyv" years="years">

In 2007, two new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), were identified in respiratory specimens from patients with respiratory illness (1,2). Since then, KIPyV and WUPyV have been frequently detected in respiratory specimens, especially those from children with respiratory symptoms and from patients co-infected with a respiratory virus (3–11). However, KIPyV and WUPyV were detected at similar rates in specimens from symptomatic patients and in persons without respiratory symptoms (6,8,12,13), suggesting that these viruses might not cause respiratory illness in immunocompetent children.
Two other human polyomaviruses, BK and JC, cause mild or asymptomatic primary infections early in life, followed by persistent, subclinical infections in healthy persons (14–16). However, these viruses can reactivate, primarily from the kidney, bone marrow, and lymphoid tissue, and cause serious disease in immunocompromised patients (14–16). Similarly, reactivation of KIPyV and WUPyV from lymphoid tissue was described among immunosuppressed persons with AIDS, although clinical consequences of reactivation were not examined (17).
Because KIPyV and WUPyV are frequently detected in association with respiratory symptoms, inhalation is suspected as a potential route of transmission. If KIPyV and WUPyV are respiratory pathogens, they may be more likely to cause respiratory illness in immunocompromised persons, either during primary infection or reactivation. Few, mostly retrospective, studies on the prevalence of KIPyV and WUPyV in respiratory specimens have included large numbers of immunocompromised patients (18–21). No prospective data are available that comprehensively describe the incidence, symptoms, risk factors, and outcomes associated with detection of KIPyV and WUPyV in respiratory specimens from hematopoietic cell transplant (HCT) recipients. This question is particularly relevant with the increasing use of multiplex PCR panels for detection of respiratory viruses, especially in samples from immunocompromised patients.
To investigate whether respiratory detection of these new polyomaviruses is associated with specific outcomes in patients after HCT, a real-time PCR specific for KIPyV and WUPyV DNA was developed and used to examine nasal wash specimens collected prospectively from HCT recipients with and without respiratory symptoms for 1 year after transplantation. Clinical data and standardized symptom surveys obtained at each specimen collection were analyzed to determine associations between respiratory KIPyV and WUPyV detection and illness.