Aberrant Epstein-Barr virus persistence in HIV carriers is characterized by anti-Epstein-Barr virus IgA and high cellular viral loads with restricted transcription

• Published in: AIDS (London) Vol. 21; no. 16; pp. 2141 - 2149
• Main Authors: STEVENS, Servi J. C, SMITS, Paul H. M, VERKUIJLEN, Sandra A. W. M, ROCKX, Davy A. P, VAN GORP, Eric C. M, MULDER, Jan W, MIDDELDORP, Jaap M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 18.10.2007
• Subjects: Adult; AIDS/HIV; Antigens, Viral - immunology; Autoradiography; Biological and medical sciences; Capsid Proteins - immunology; DNA, Viral - blood; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - virology; Epstein-Barr Virus Nuclear Antigens - immunology; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - physiology; HIV Seropositivity - immunology; HIV Seropositivity - virology; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin A - blood; Immunopathology; Infectious diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - virology; Medical sciences; Transcription, Genetic; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virus Latency; IgA; Transcription; Mucosa; Epstein Barr virus; Microbiological investigation; Nucleic acid sequence-based amplification; Lymphoproliferative syndrome; Epstein-Barr virus; Viral load; Gammaherpesvirinae; Immunopathology; Herpesviridae; AIDS; Malignant hemopathy; B-Lymphocyte; Immune deficiency; Lymphoma; Latency; Infection; Virus; Polymerase chain reaction; HIV; Viral disease; viral; Molecular biology; ELISA assay
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e3282eeeba0

Epstein-Barr virus (EBV)-positive lymphomas in HIV carriers are paralleled by elevated EBV-DNA loads in the circulation. Approximately 20% of asymptomatic HIV carriers also show elevated circulating EBV-DNA loads. We aimed to characterize the nature of this EBV DNA and to determine the transcriptional phenotype of EBV in blood, in relation to serological parameters. A total of 197 random asymptomatic HIV carriers, representing 2% of the Dutch HIV-positive population, were sampled for blood, peripheral blood mononuclear cells and plasma. In addition, 39 EBV-DNA carriers were sampled twice, with a 5-year interval. EBV-DNA loads were determined by LightCycler-based real-time polymerase chain reaction (PCR). EBV transcription was studied by nucleic acid sequence-based amplification and reverse transcriptase PCR. IgA and IgG antibodies to EBV antigens EBNA1 and VCA-p18 were quantified by synthetic peptide-based enzyme-linked immunosorbent assay. : Elevated EBV-DNA loads were found in whole blood of 19.3% of the tested HIV population, which were persistent in 82%. Plasma samples were EBV-DNA negative and circulating EBV DNA could be attributed to the B-cell compartment. Transcription of only LMP2 and (non-translated) transcripts from the BamHI-A region of the EBV genome was found, whereas EBNA1, LMP1 and lytic EBV transcripts were absent despite high cellular EBV-DNA loads. IgA-reactivity to VCA-p18 was seen in 69%. IgG to VCA-p18 was significantly higher in high EBV-DNA load carriers. Asymptomatic HIV carriers show aberrant EBV persistence in the circulation, characterized by elevated, B-cell-associated EBV-DNA loads. EBV transcription is restricted, arguing for EBV gene shutdown in circulating EBV-carrying B cells. Increased IgA and IgG reactive to VCA-p18 is indicative of increased lytic EBV replication, possibly occurring at mucosal lymphoid sites but not in the circulation.