ABSTRACT
BACKGROUND: In search of a proposed viral aetiology of childhood acute lymphoblastic leukaemia (ALL), the common species C adenoviruses were analysed in Guthrie cards. METHODS: Guthrie cards from 243 children who later developed ALL and from 486 matched controls were collected and analysed by nested polymerase chain reaction for the presence of adenovirus DNA. RESULTS: Adenovirus DNA was reliably detected from only two subjects, both of whom developed ALL. CONCLUSION: Adenovirus DNA is detected in Guthrie card samples at too low a frequency to reveal an association between adenovirus and the development of leukaemia.
Subject(s)
Adenoviridae Infections/virology , Adenoviridae/genetics , DNA, Viral/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology , Adenoviridae Infections/diagnosis , Adenoviridae Infections/genetics , Adolescent , Case-Control Studies , Child , Child, Preschool , Female , Humans , Infant , Male , Polymerase Chain Reaction , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , PrognosisABSTRACT
An artificial antigen composed of 12 small antigenic regions derived from the ORF2 and ORF3 HEV proteins was designed. The gene encoding for this artificial antigen was assembled from synthetic oligonucleotides by a new method called Restriction Enzyme-Assisted Ligation (REAL). The diagnostic relevance of this second generation HEV mosaic protein (HEV MA-II) was demonstrated by testing this antigen against a panel of 142 well defined anti-HEV positive and anti-HEV negative serum samples. The data obtained in this study support the substantial diagnostic potential of this HEV mosaic antigen.
Subject(s)
Hepatitis Antigens/immunology , Hepatitis E virus/immunology , Hepatitis E/diagnosis , Recombinant Proteins/immunology , Viral Proteins/immunology , Amino Acid Sequence , Animals , Base Sequence , Hepatitis Antibodies/blood , Hepatitis Antibodies/immunology , Hepatitis Antigens/genetics , Hepatitis E/immunology , Humans , Mice , Molecular Sequence Data , Oligonucleotides/chemical synthesis , Protein Engineering , Recombinant Proteins/genetics , Viral Proteins/geneticsABSTRACT
Although species C human adenoviruses establish persistent infections, the molecular details of this lifestyle remain poorly understood. We previously reported that adenovirus DNA is found in human mucosal T lymphocytes in a noninfectious form (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol. 76:10608-10616, 2002). In this study, human tonsil and adenoid tissues were analyzed to determine the dynamics of infection, the rate of clearance of viral DNA, and the possibility of reactivation of virus from these tissues. The presence of viral DNA peaked at 4 years of age and declined thereafter. The average number of viral genomes declined with the age of the donor. The frequency of virus-bearing cells ranged from 3 x 10(-7) to 3.4 x 10(-4), while the amount of viral DNA per cell varied less, with an average of 280 copies per cell. All species C serotypes were represented in these tissues, although adenovirus type 6 was notably rare. Infectious virus was detected infrequently (13 of 94 of donors tested), even among donors with the highest levels of adenoviral DNA. Adenovirus transcripts were rarely detected in uncultured lymphocytes (2 of 12 donors) but appeared following stimulation and culture (11 of 13 donors). Viral DNA replication could be stimulated in most donor samples by lymphocyte stimulation in culture. New infectious virus was detected in 13 of 15 donors following in vitro stimulation. These data suggest that species C adenoviruses can establish latent infections in mucosal lymphocytes and that stimulation of these cells can cause viral reactivation resulting in RNA transcription, DNA replication, and infectious virus production.
Subject(s)
Adenoviridae/isolation & purification , Adenovirus Infections, Human/virology , Carrier State/virology , DNA, Viral/isolation & purification , Palatine Tonsil/virology , Virus Latency , Adenoviridae/classification , Adenoviridae/physiology , Adolescent , Age Factors , Cells, Cultured , Child , Child, Preschool , Humans , Lymphocytes/virology , Serotyping , Virus ActivationABSTRACT
Epidemiological evidence suggests that childhood acute lymphoblastic leukaemia (ALL) may be initiated by an in infection in utero. Adenovirus DNA was detected in 13 of 49 neonatal blood spots from ALL patients but only in 3 of 47 controls (P=0.012) suggesting a correlation between prenatal adenovirus infection and the development of ALL.
