Adenovirus (AdV) infections are a major cause of morbidity and mortality in allogeneic stem cell transplant (SCT) recipients. Human adenoviruses represent a large family, currently including 51 serotypes, which are divided into 6 species (A-F). We have recently demonstrated by a species-specific RQ-PCR approach covering the entire spectrum of human adenoviruses that molecular detection of AdV in peripheral blood precedes the onset of life-threatening virus disease, and provides a basis for early preemptive treatment (

Lion et al., Blood 102(3):1114–20, 2003
). An association of AdV species with clinical manifestation and response to antiviral therapy has been reported, but little is known about the clinical role of individual AdV serotypes. In immunocompromised patients, the use of serological testing for identification of adenovirus serotypes is limited due to the impaired immune response. We have therefore determined the nucleotide sequence of the complete AdV hexon gene in all 51 human serotypes, and identified regions permitting rapid serotyping at the molecular level. Serotypes belonging to the species A,B, C, E, and F, can be determined by fragment length analysis of a single PCR product, respectively. Serotype identification within the largest AdV species D requires sequencing of a single 300bp PCR amplicon. In view of the great predominance of species C in our region, we have also established real-time PCR tests permitting identification of its four serotypes. Analysis of all AdV C positive cases within more than 6.000 clinical specimens investigated at our center over the past years revealed the highest prevalence for serotype 2 (57%), followed by the serotypes 1 (39%) and 5 (4%). In some instances, two different AdV C serotypes were present simultaneously. We have demonstrated that the identification of specific virus strains within individual AdV serotypes, which may be required for investigation of possible transmission of infections within the hospital, can be achieved by sequencing of PCR products derived from an appropriate AdV target region within the hexon gene. The possibility of rapid molecular serotype and strain analysis provides a basis for studies on adenovirus epidemiology, and may in future have implications for the selection of the most appropriate antiviral treatment.

Topics:
adenoviruses, allogeneic stem cell transplant, antiviral agents, infections, polymerase chain reaction, serologic tests, serotype, serotyping, signs and symptoms, virus diseases

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2005, The American Society of Hematology
2004
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