Chronic norovirus infection after kidney transplantation: molecular evidence for immune-driven viral evolution.
BACKGROUND
Norovirus infection is the most common cause of acute self-limiting gastroenteritis. Only 3 cases of chronic norovirus infection in adult solid organ transplant recipients have been reported thus far.


METHODS
This case series describes 9 consecutive kidney allograft recipients with chronic norovirus infection with persistent virus shedding and intermittent diarrhea for a duration of 97-898 days. The follow-up includes clinical course, type of immunosuppression, and polymerase chain reaction for norovirus. Detailed molecular analyses of virus isolates from stool specimens over time were performed.


RESULTS
The intensity of immunosuppression correlated with the diarrheal symptoms but not with viral shedding. Molecular analysis of virus strains from each patient revealed infection with different variants of GII.4 strains in 7 of 9 patients. Another 2 patients were infected with either the GII.7 or GII.17 strain. No molecular evidence for nosocomial transmission in our outpatient clinic was found. Capsid sequence alignments from follow-up specimens of 4 patients showed accumulation of mutations over time, resulting in amino acid changes predominantly in the P2 and P1-2 region. Up to 25 amino acids mutations were accumulated over a 683-day period in the patient with an 898-day shedding history.


CONCLUSIONS
Norovirus infection may persist in adult renal allograft recipients with or without clinical symptoms. No evidence for nosocomial transmission in adult renal allograft recipients was found in our study. Molecular analysis suggests continuous viral evolution in immunocompromised patients who are unable to clear this infection.
Schorn
Robert
R
Divisions of Nephrology, University Hospital, Zurich, Switzerland.
Höhne
Marina
M
Meerbach
Astrid
A
Bossart
Walter
W
Wüthrich
Rudolf P
RP
Schreier
Eckart
E
Müller
Nicolas J
NJ
Fehr
Thomas
T
D000328:Adult; D017250:Caliciviridae Infections / Q000175:diagnosis / Q000821:virology*; D002908:Chronic Disease; D016000:Cluster Analysis; D003967:Diarrhea / Q000175:diagnosis / Q000821:virology; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D029322:Norovirus / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
D012367:RNA, Viral