Posttransplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus.
Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are seen in immunocompromised hosts and in many lymphoid neoplasms associated with immunocompromise. The posttransplantation lymphoproliferative disorders (PT-LPDs) are a heterogeneous group of B-cell neoplasms that arise in the setting of immunosuppressive therapy, and are associated with EBV infection. Whether type A and/or type B EBV are associated with PT-LPDs is unknown. Therefore, we investigated 27 PT-LPD lesions from 22 solid-organ transplant recipients by polymerase chain reaction (PCR) at the EBNA-2 and EBNA-3c loci to detect sequence deletions that distinguish the two EBV families. Another locus, EBER, was examined by single-strand conformation polymorphism analysis (SSCP), in conjunction with direct sequencing in selected cases. Type A EBV was found in 24 of 27 cases (89%) as seen by amplification of the EBNA-2 and EBNA-3c regions. Four different EBER polymorphisms were detected, confirming the presence of different type A EBV isolates among these cases. Three cases were negative for infection by EBV. Surprisingly, despite the immunocompromised state of the hosts, none of the 27 PT-LPD lesions harbored type B EBV. Thus, although type B EBV may commonly infect peripheral blood lymphocytes in immunocompromised individuals, they do not appear to induce readily PT-LPD formation.
Frank
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Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY, 10021.
Cesarman
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Liu
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Michler
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Knowles
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DM
D000956:Antigens, Viral / Q000235:genetics; D001402:B-Lymphocytes / Q000821:virology; D001483:Base Sequence; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D016867:Immunocompromised Host; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000821:virology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011183:Postoperative Complications / Q000821:virology*; D014180:Transplantation; D015678:Viral Structural Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics
D000956:Antigens, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D015678:Viral Structural Proteins