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Epstein-Barr Virus Associated Disorders

$861,221ZIAFY2021AINIH

National Institute Of Allergy And Infectious Diseases

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Abstract

Epstein-Barr virus (EBV) is the major cause of infectious mononucleosis and is associated with both B cell cancers (Hodgkin lymphoma, Burkitt lymphoma) and epithelial cell cancers (nasopharyngeal carcinoma, gastric carcinoma). The virus typically infects epithelial cells of the oropharynx and B cells circulating in the blood. The virus establishes a latent infection in B cells where it persists for life. Maternal antibody is thought to prevent EBV infection. Maternal HIV infection is associated with an increased incidence of EBV infection in exposed infants, which is thought to be due to impaired transfer of EBV-neutralizing maternal antibodies. In FYI 2021, we followed Ugandan infants for EBV acquisition from birth and measured antibodies in plasma samples of infants before they were infected. We quantified antibodies important for (a) binding to EBV glycoproteins (gp350, gH/gL) involved in B-cell and epithelial-cell entry, (b) EBV neutralization, and (c) antibody-dependent cellular cytotoxicity which is important for killing virus-infected cells. Antibody levels were analyzed for differences between HIV-exposed uninfected and HIV-unexposed infants, and for associations with infant EBV infection. HIV-exposed uninfected infants had significantly higher antibody titers than HIV unexposed infants for all EBV-binding and neutralizing antibodies measured (P < .01), but not for antibody-dependent cellular cytotoxicity which was similar between the two groups. No antibody measure was associated with a decreased risk of EBV acquisition in these infants. Our findings indicate that in this cohort, maternal antibody did not protect infants against EBV infection through viral neutralization. The identification of protective antibody functions would be important for the development of an EBV vaccine.

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