Discrimination of Antibody to Herpes B Virus from Antibody to Herpes Simplex Virus Types 1 and 2 in Human and Macaque Sera

Abstract

The antigenic cross-reactive characteristics of herpes B virus and herpes simplex virus (HSV) type 1 (HSV-1) and HSV-2 are responsible for false-positive diagnoses by serological assays in humans and macaques. In the present study, we developed a fluorometric indirect enzyme-linked immunosorbent assay (ELISA) with recombinant herpes B virus glycoprotein D (gD) and HSV-1 and HSV-2 gG (gG-1 and gG-2, respectively) to discriminate between the three primate herpesvirus infections. The secreted form of gD, gDdTM, was used to detect antibody to herpes B virus gD. Sera positive for herpes B virus, HSV-1, and HSV-2 showed specific reactions to gD, gG-1, and gG-2, respectively. Sera collected from humans and rhesus macaques were investigated for the presence of antibodies to the recombinant proteins of the three herpesviruses. The results suggested that the approach is able to discriminate between herpes B virus and HSV infections. The ELISA was also found to be able to detect infections with multiple primate herpesviruses and may have the potential to identify a subsequent infection in individuals that have already been infected with another herpesvirus. In addition, we found evidence of a greater cross-reactivity of herpes B virus with HSV-1 than with HSV-2. It is suggested that the ELISA with the recombinant antigens is useful not only for the serodiagnosis of primate herpesvirus infections but also for elucidation of the seroprevalence of herpesviruses in humans and primates.Herpes B virus (Cercopithecine herpesvirus 1) infection is a fatal zoonosis characterized by acute encephalomyelitis (26,27). The rate of mortality among individuals with the infection is high if such individuals are not given antiviral therapy in the early stages of infection. The natural hosts of the causative agent are Asian macaques, which are used in the medical field as models for humans. This suggests that laboratory workers in contact with the macaques could become exposed to viruscontaminated sources, such as saliva and urine from infected hosts (4). Therefore, the development of a rapid and accurate method for the detection of herpes B virus infection is required for both the early diagnosis of the infection in patients and the establishment of virus-free macaque colonies. Serological assays, including enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB) analysis with a herpes B virusinfected cell antigen, are available for the detection of herpes B virus infections (2,7,12,18).The serodiagnosis of herpes B virus infections is difficult because of the antigenic cross-reactivity of herpes B virus with related herpesviruses. Herpes B virus is classified as a member of the subfamily Alphaherpesvirinae, which includes herpes simplex virus (HSV) type 1 (HSV-1) and HSV-2, and has been shown to share antigenic and biological characteristics with these human herpesviruses, such as a tropism for neurons and propagation and dissemination in natural hosts (6,8,21). The high seroprevalence of HSV in humans, which has been reported to...

Specific pathogen free macaque colonies: a review of principles and recent advances for viral testing and colony management

“…BV recombinant glycoproteins have recently become available for incorporation in these tests for improving the diagnostic potential and screening standardization. ELISAs utilizing multiple recombinant glycoprotein antigens (gB, gC, gD, and membrane‐associated gG) were reported to provide the highest sensitivity and specificity . In addition, the gG antigen was useful in discriminating between BV and other closely related alphaherpesviruses .…”

Deconvoluting Virome-Wide Antiviral Antibody Profiling Data

“…The diagnostic and epidemiologic utility of antibody analyses has been limited in large part due to the difficulty in accounting for antibody cross reactivities among closely related organisms 10 . The development of an analytical framework that accounts for potential cross reactivity in pan-viral serological data, and which provides probabilistic assessments of infections, is therefore an important advance.…”

“…The utility of antibody-based diagnostics has been constrained by an inability to robustly discriminate among infections by closely related viral pathogens 10 . An important example is the challenge of distinguishing between flavivirus infections, notably in the setting of the recent Zika virus outbreak 11 .…”

Optimized Expression, Purification of Herpes B Virus gD Protein in Escherichia coli, and Production of Its Monoclonal Antibodies

“…According to previous studies ( 38 ), for the diagnosis of many viral infections, recombinant DNA techniques generally play an important role. However, the use of recombinant antigens for BV sero-diagnosis has not been widely investigated, and it has been proposed that the specificity of BV gD is probably a valuable diagnostic reagent for distinguishing herpes B virus infections ( 23 , 39 , 40 ).…”