Immune Reactivity of Human Sera to the Glycoprotein B of Human Herpesvirus 7

Abstract

The glycoprotein B (gB) is highly conserved among distinct human herpesvirus 7 (HHV-7) strains. Similarly to other herpesvirus glycoproteins, gB has been assumed to induce a specific human immune response. However, it did not appear as an immunodominant protein in conventional immunoblot assays. Recombinant gB, obtained from either Escherichia coli or baculovirus expression systems, did react specifically with HHV-7-seropositive sera, and the main corresponding epitopes were located in its N-terminal part. A 24-amino-acid peptide, corresponding to a predicted hydrophilicity peak and presenting no extensive homology with other betaherpesvirus glycoproteins, was selected in this region at positions 129 to 152 of the gB sequence. When tested by enzyme-linked immunosorbent assay (ELISA), this peptide specifically reacted with HHV-7-seropositive sera. This reactivity was significantly inhibited by the preincubation of sera with the peptide itself, lysates of gB-expressing cells, or lysates of HHV-7-infected cells. The reactivity was not significantly modified when sera were preincubated with lysates of either human cytomegalovirus (HCMV)-or HHV-6-infected cells. In cross-sectional studies including both children and adults, 49 out of 61 serum samples (80%) were found to be positive by HHV-7 ELISA, independent of their reactivity to HCMV. A longitudinal serological study of 17 children during the first 4 years of life showed that the level of ELISA-detected antibodies significantly decreased within a few weeks after birth and then increased in the following months, likely reflecting, respectively, the loss of maternal antibodies and the occurrence of seroconversion. These results demonstrate that gB peptide ELISA might be a useful tool for the serological study of HHV-7 infection.Human herpesvirus 7 (HHV-7) is a recently recognized herpesvirus, isolated initially from the peripheral blood lymphocytes of healthy individuals (18). HHV-7 prevalently infects individuals at young ages (1,24,28,47,48) and persistently infects CD4 ϩ T lymphocytes (2, 19, 25) as well as salivary glands (31). The virus is excreted in saliva (21, 46), which is the most likely route of transmission. The natural history of HHV-7 infection in the human host is not well known. Primary infection has not yet been consistently associated with a given disease, and the potential association of HHV-7 reactivation with diseases in adults remains to be confirmed (11,22,32,33,40,43,45).These pending questions point out the need for relevant diagnostic tools targeted to HHV-7 infection. So far, the serological diagnosis of HHV-7 infection has raised concerns about its specificity (3, 14, 38) because HHV-7 has marked homologies with the two other human betaherpesviruses, HHV-6 and, to a lesser extent, human cytomegalovirus (HCMV). The cross-reactive human antibodies have to be removed by preadsorption with heterologous virus antigens, which strongly affects the feasibility, reproducibility, and sensitivity of serological HHV-7 assays. Several attempts have re...

Human Herpesviruses 6, 7 and 8 in Solid Organ Transplant Recipients

“…Viral culture may be performed on peripheral blood mononuclear cells but this is very laborious and is only available in research laboratories. Serology is of limited clinical utility due to the ubiquitous nature of HHV‐7 infection in humans, and transplant patients generally are not able to generate antibodies in a rapid and efficient manner .…”

Identification and Expression of Immunogenic Proteins of a Disease-Associated Marine Turtle Herpesvirus

“…A second LETV protein, glycoprotein B (gB), was also selected for cloning and expression. gB has been identified as a major target of the antiherpesvirus immune response in many host species and includes virus-neutralizing activity (6,12,19). gB also has been extensively targeted for the development of many mammalian herpesvirus vaccines and for the development of serological assays for detection of herpesvirus infections (1,5,7,13,14).…”