Identification of unique B virus (Macacine Herpesvirus 1) epitopes of zoonotic and macaque isolates using monoclonal antibodies

• Published in: PloS one Vol. 12; no. 8; p. e0182355
• Main Authors: Katz, David, Shi, Wei, Gowda, Manjunath S, Vasireddi, Mugdha, Patrusheva, Irina, Seoh, Hyuk-Kyu, Filfili, Chadi N, Wildes, Martin J, Oh, Jay, Hilliard, Julia K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.08.2017; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antigens; Biology; Biology and life sciences; Cercopithecine herpesvirus 1; Competition; Diagnosis; Differential diagnosis; Epitopes; Epitopes - immunology; Glycoprotein B; Glycoprotein D; Glycoproteins; Health aspects; Herpes viruses; Herpesvirus 1, Cercopithecine - immunology; Herpesvirus 1, Cercopithecine - isolation & purification; Humans; Immunoglobulins; Immunology; Infection; Infections; Laboratories; Macaca fascicularis; Macaca mulatta; Medicine and Health Sciences; Mice; Monoclonal antibodies; Patients; Proteins; Reagents; Recombinant Proteins - immunology; Research and Analysis Methods; Rhesus monkey; Ultraviolet radiation; Viral Envelope Proteins - immunology; Viruses; Zoonoses; Zoonoses - virology; Atlanta Georgia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182355

Our overall aim is to develop epitope-based assays for accurate differential diagnosis of B virus zoonotic infections in humans. Antibodies to cross-reacting epitopes on human-simplexviruses continue to confound the interpretation of current assays where abundant antibodies exist from previous infections with HSV types 1 and 2. To find B virus-specific epitopes we cloned ten monoclonal antibodies (mAbs) from the hybridomas we produced. Our unique collection of rare human sera from symptomatic and asymptomatic patients infected with B virus was key to the evaluation and identification of the mAbs as reagents in competition ELISAs (mAb-CE). The analysis of the ten mAbs revealed that the target proteins for six mAbs was glycoprotein B of which two are reactive to simian simplexviruses and not to human simplexviruses. Two mAbs reacted specifically with B virus glycoprotein D, and two other mAbs were specific to VP13/14 and gE-gI complex respectively. The mAbs specific to VP13/14 and gE-gI are strain specific reacting with B virus isolates from rhesus and Japanese macaques and not with isolates from cynomolgus and pigtail macaques. The mAb-CE revealed that a high proportion of naturally B virus infected rhesus macaques and two symptomatic humans possess antibodies to epitopes of VP13/14 protein and on the gE-gI complex. The majority of sera from B virus infected macaques and simplexvirus-infected humans competed with the less specific mAbs. These experiments produced a novel panel of mAbs that enabled B virus strain identification and confirmation of B virus infected macaques by the mAb-CE. For human sera the mAb-CE could be used only for selected cases due to the selective B virus strain-specificity of the mAbs against VP13/14 and gE/gI. To fully accomplish our aim to provide reagents for unequivocal differential diagnosis of zoonotic B virus infections, additional mAbs with a broader range of specificities is critical.