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


METHODS
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.


METHODS
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.


RESULTS
: 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.


CONCLUSIONS
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.
Stevens
Servi J C
SJ
Department of Pathology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
Smits
Paul H M
PH
Verkuijlen
Sandra A W M
SA
Rockx
Davy A P
DA
van Gorp
Eric C M
EC
Mulder
Jan W
JW
Middeldorp
Jaap M
JM
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D001345:Autoradiography; D036022:Capsid Proteins / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000821:virology*; D014158:Transcription, Genetic; D019562:Viral Load; D017735:Virus Latency
D000956:Antigens, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; C041788:Epstein-Barr viral capsid antigen; D007070:Immunoglobulin A