TABLE 1.

Diagnostic methods for EBV detection

MethodAnalyte, antigen, or substrateComment
Serology
    IFACell lines like P3HR-1 and RajiClassical method; gold standard; highly specific; staging of EBV infections possible with a single serum sample
    Complement fixation reactionLysate of EBV-transformed cell linesLess sensitive, less specific; not widely used; staging of EBV infections not possible with a single serum sample
    EIA, ELISA, or chemoluminescence with coated beadsLysate of EBV-transformed cell lines; EBV lysates; combination of lysates and recombinant proteins; recombinant proteins; synthetic peptidesRapid, highly sensitive, suitable for automation; synthetic peptides as antigens less sensitive and less specific (due to cryptic epitopes in native molecules); with a single serum sample
    Blot techniques (Western blot analysis or line blot assays)Lysate of EBV-transformed cell lines; EBV lysates; recombinant proteins; combination of lysates and recombinant proteinsHighly specific; mostly a confirmatory method; staging of EBV infections possible with a single serum sample
    IgG avidity determination, IFA, and/or ELISA or Western blot analysisTitration of antibodies in the absence and presence of increasing amounts of urea or other chaotropic reagentsRather special method used for confirmation of indeterminate results (Table 2) (antibodies in an acute EBV infecti on are of low avidity)
    Heterophile antibody agglutinationPaul-Bunnell antigens; bovine erythrocytesLess sensitive, less specific; 10-50% of children <4 years of age do not produce heterophile antibodies
Virus isolationLymphoblastoid cell lines from patient lymphocytesPerformed only in special laboratories; long-lasting test (up to 4-8 weeks)
Nucleic acid detection
    PCRLymphocytes, plasma, serum, cerebrospinal fluid, tissueMethod of choice if EBV-associated meningoencepahlitis (from cerebrospinal fluid) is suspected; used to detect virus load and reactivation
    In situ hybridization, in situ PCRTumor tissue; paraffin-embedded sectionsUsed to detect EBV-associated tumors
Virus antigens, immunhistochemistry and immunocytologyTumor tissue; paraffin-embedded sectionsUsed to detect EBV-associated tumors