Presence of adenovirus species C in infiltrating lymphocytes of human sarcoma

TY - JOUR

T1 - Presence of adenovirus species C in infiltrating lymphocytes of human sarcoma

AU - Kosulin, Karin

AU - Hoffmann, Franziska

AU - Clauditz, Till Sebastian

AU - Wilczak, Waldemar

AU - Dobner, Thomas

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Human adenoviruses are known to persist in T-lymphocytes of tonsils, adenoids and intestinal tract. The oncogenic potential of different adenovirus types has been widely studied in rodents, in which adenovirus inoculation can induce multiple tumors such as undifferentiated sarcomas, adenocarcinomas and neuroectodermal tumors. However, the oncogenic potential of this virus has never been proven in human subjects. Using a highly sensitive broad-spectrum qRT-PCR, we have screened a set of different human sarcomas including leiomyosarcoma, liposarcoma and gastro intestinal stroma tumors. Primers binding the viral oncogene E1A and the capsid-coding gene Hexon were used to detect the presence of adenovirus DNA in tumor samples. We found that 18% of the tested leiomyosarcomas and 35% of the liposarcomas were positive for the presence of adenovirus DNA, being species C types the most frequently detected adenoviruses. However, only in one sample of the gastro intestinal stroma tumors the virus DNA could be detected. The occurrence of adenovirus in the tumor sections was confirmed by subsequent fluorescence in-situ-hybridization analysis and co-staining with the transcription factor Bcl11b gives evidence for the presence of the virus in infiltrating T-lymphocytes within the tumors. Together these data underline, for the first time, the persistence of adenovirus in T-lymphocytes infiltrated in muscular and fatty tissue tumor samples. If an impaired immune system leads to the viral persistence and reactivation of the virus is involved in additional diseases needs further investigation.

AB - Human adenoviruses are known to persist in T-lymphocytes of tonsils, adenoids and intestinal tract. The oncogenic potential of different adenovirus types has been widely studied in rodents, in which adenovirus inoculation can induce multiple tumors such as undifferentiated sarcomas, adenocarcinomas and neuroectodermal tumors. However, the oncogenic potential of this virus has never been proven in human subjects. Using a highly sensitive broad-spectrum qRT-PCR, we have screened a set of different human sarcomas including leiomyosarcoma, liposarcoma and gastro intestinal stroma tumors. Primers binding the viral oncogene E1A and the capsid-coding gene Hexon were used to detect the presence of adenovirus DNA in tumor samples. We found that 18% of the tested leiomyosarcomas and 35% of the liposarcomas were positive for the presence of adenovirus DNA, being species C types the most frequently detected adenoviruses. However, only in one sample of the gastro intestinal stroma tumors the virus DNA could be detected. The occurrence of adenovirus in the tumor sections was confirmed by subsequent fluorescence in-situ-hybridization analysis and co-staining with the transcription factor Bcl11b gives evidence for the presence of the virus in infiltrating T-lymphocytes within the tumors. Together these data underline, for the first time, the persistence of adenovirus in T-lymphocytes infiltrated in muscular and fatty tissue tumor samples. If an impaired immune system leads to the viral persistence and reactivation of the virus is involved in additional diseases needs further investigation.

KW - Adenovirus E1A Proteins

KW - Adenoviruses, Human

KW - Base Sequence

KW - Host-Pathogen Interactions

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Leiomyosarcoma

KW - Liposarcoma

KW - Molecular Diagnostic Techniques

KW - Molecular Sequence Data

KW - Molecular Typing

KW - Real-Time Polymerase Chain Reaction

KW - Sequence Analysis, DNA

KW - T-Lymphocytes

KW - Viral Load

U2 - 10.1371/journal.pone.0063646

DO - 10.1371/journal.pone.0063646

M3 - SCORING: Journal article

C2 - 23671688

VL - 8

SP - e63646

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 5

ER -