Immune Response to Neutralizing Epitope on Human Cytomegalovirus Glycoprotein B in Japanese: Correlation of Serologic Response with HLA‐Type

Abstract

Antigenic domain 1 (AD-1), located between amino acids 608 and 625 of human cytomegalovirus (CMV) gB protein, is the major domain recognized by neutralizing antibodies. Amino acids 552 to 630 are essential for the binding of neutralizing antibodies. We developed an enzyme-linked immunosorbent assay (ELISA) to detect antibodies against a fusion protein containing amino acid residues 549 to 644 of the gB polypeptide and maltose binding protein (MBP). Of 180 seropositive samples, 106 (58.9%) showed positive immuno-reactivity against the fusion protein. None of the seronegative samples reacted with the fusion protein. Among 57 seropositive individuals typed for HLA, subjects with HLA-DR9 had a higher positive rate against the fusion protein (13/14=92.9%) than those without HLA-DR9 (25/43=58.1%). In addition, subjects with HLA-DR15 had a lower positive rate against the fusion protein (7/16=43.3%) than those without HLA-DR15 (31/41=75.6%). Mean OD values of HLA-DR15-positive individuals were significantly lower than those of HLA-DR15-negative individuals. Thus, among CMV-infected individuals, HLA-DR9 may be associated with responders for neutralizing antibodies and HLA-DR15 may be associated with non/lowresponders.

An antigen fragment encompassing the AD2 domains of glycoprotein B from two different strains is sufficient for differentiation of primary vs. recurrent human cytomegalovirus infection by ELISA

“…Kropff et al [1993] reported a low prevalence of 44% of AD1-ELISA reactive antibodies in serum specimens with low titers of neutralizing antibodies. Wada et al [1997] found a seroprevalence of 59% in HCMV seropositive individuals using a similar ELISA approach. This is consistent with results described in this communication concerning the reactivity of serum samples from HCMV seropositive blood donors with either procaryotically expressed AD1 or an AD1peptide.…”

Human Herpesvirus 6 and Multiple Sclerosis: Systemic Active Infections in Patients with Early Disease

“…P ! .035 Therefore, it appears that patients with MS have an unusual and perhaps genetically influenced [53][54][55] immunologic relationship with HHV-6 in that they are even less able to effectively control their active HHV-6 infections than are other patients receiving severe iatrogenic immunosuppressive therapy.…”

Role of Cytomegalovirus Reinfection in Acute Rejection and CMV Disease After Renal Transplantation

“…Another possible association between HLA and CMV infection is in the production of antibodies. It has been reported that deficiencies in the production of neutralizing antibodies against CMV gB in certain HLA types may lead to increased susceptibility (Wada, Mizuno et al 1997). In this report, subjects with HLA-DR9 had a higher positive rate against CMV gB and subjects with HLA-DR15 had a lower positive rate against gB.…”