PRIMARY HUMAN HERPESVIRUS TYPE 8 (HHV-8) INFECTION OCCURS FOLLOWING ADOLESCENCE IN THE UNITED STATES

Abstract

Background: Most recent evidence suggests that infection with the newly described γ-herpesvirus, HHV-8, also known as Kaposi's sarcoma(KS)-associated herpesvirus, is restricted to individuals at risk for developing KS. The prevalence of infection in the general population remains controversial. Thus, to more accurately determine the age of primary infection, we examined children and adults (all individuals had AIDS and no clinical sign of KS) for evidence of HHV-8 infection, hypothesizing that HHV-8, like other herpesviruses, may be more readily detected in the setting of advanced immunosuppression. Methods: Peripheral blood mononuclear cell (PBMC) DNA and sera were obtained from 84 U.S. AIDS patients, including 49 children (median age=6) and 35 adults. Nested PCR, using nonoverlapping primers specific for HHV-8, Epstein-Barr virus (EBV), and cytomegalovirus (CMV), and immunofluorescence (IF)/ELISA assays were used to detect virus-specific DNA and antibodies, respectively. Results: In pediatric AIDS patients, EBV- and CMV-specific DNA was detected in 22/49 (43%) and 9/49 (18%) PBMC, respectively. Strikingly, HHV-8 DNA was not detected in a single sample (0/49), in otherwise identical assays performed in parallel. Antibodies directed against HHV-8 antigens expressed in latently-infected cells were not detected in sera from the children by IF, whereas 1/49 (2%) children had antibodies directed against an HHV-8 antigen expressed in lytically-infected cells by ELISA. By contrast, in adult AIDS patients, we detected HHV-8 DNA in 8/35 (23%) PBMC. In summary, most U.S. children showed no evidence of HHV-8 infection using all currently accepted detection methods. Conclusion: This is the first comparative study of HHV-8 detection in the blood of immunocompromised children and adults. Our findings suggest that the pattern of transmission of HHV-8 in the general U.S. population differs from other herpesviruses in that infection occurs predominantly in years following adolescence.