Antigenic Differences between HSV-1 and HSV-2 Glycoproteins and Their Importance for Type-Specific Serology

Abstract

The ability to discriminate between herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) infections by serological means is of increasing importance for clinical virological diagnostics. HSV type-specific serology has a number of applications, e.g. to guide duration and dosage of antiviral therapy, to allow for stringent epidemiological analyses, to evaluate efficacy of HSV vaccine candidates, and to help the clinician during counseling of couples where one has genital herpes. The genomes of the two HSV types appear to be sufficiently intratypically stable and intertypically discrepant to permit such a discrimination. Despite recent advances in methodology, the ideal HSV type-specific serological assays still remain to be developed. The viral antigens utilized for such an assay should evoke strong antibody responses, but only against unique determinants, in order to be able to combine high sensitivity and specificity. Of all the HSV envelope proteins, the most promising candidate antigens, i.e. HSV-1 glycoprotein G (gG-1) and its HSV-2 counterpart gG-2, contain relatively long type-unique stretches of amino acids. However, whether the type-specific determinants preferentially localize to the unique or homologous stretches of gG is still unknown. Paradoxically, type-specific monoclonal antibodies to the moderately type-specific antigen, HSV-1 glycoprotein C, have hitherto been mapped to homologous rather than to type-unique stretches. A definition of human type-specific epitopes on gG-1 and gG-2, as well as a broader search for new candidate HSV antigens, might be needed to fully discriminate dual infections from high titer single HSV-1 or HSV-2 infections.

Localization of type-specific epitopes of herpes simplex virus type 2 glycoprotein G recognized by human and mouse antibodies.

“…In HSV infection, antibodies to gG are readily detected, and can effectively discriminate between HSV-1 and HSV-2 (for a review see Bergstro$ m & Trybala, 1996). The nature of this type-specific sero-reactivity is hitherto unknown, but the unique regions existing in gG-1 and gG-2 (McGeoch et al, 1985(McGeoch et al, , 1987 could be expected to harbour HSV-1-and HSV-2-type-specific epitopes, respectively.…”

“…Liljeqvist and others J.-A H . Liljeqvist and others region with an extensive amino acid homology with HSV-2 gC (Bergstro$ m & Trybala, 1996 ;Wu et al, 1990). Within this homologous region of gG-2 a stretch of amino acid residues was found with which all purified human anti-gG-2 antibodies (but none of the purified anti-gG-1 antibodies), as well as three anti-gG-2 MAbs, were reactive.…”

Dichotomy of Glycoprotein G Gene in Herpes Simplex Virus Type 1 Isolates

“…The ability to discriminate between HSV-1 and HSV-2 infections by serological means has been of importance for several clinical aspects, including diagnosis and treatment of neonatal herpes as well as of complications from the central nervous system (5,7,9,10,23). Glycoprotein G-1 (gG-1), a viral envelope glycoprotein (1,21) that was suggested to contribute to viral entry through apical surfaces of polarized cells (33), has been utilized as a prototype antigen for HSV-1 type-specific diagnosis due to lack of crossreactivity with its counterpart in HSV-2, i.e., gG-2 (15,29).…”

Use of a Fragment of Glycoprotein G-2 Produced in the Baculovirus Expression System for Detecting Herpes Simplex Virus Type 2-Specific Antibodies

“…This homologous sequence comprises the part adjacent to the transmembrane region and the cytoplasmic domain. gG-2 is cleaved during processing into an amino-terminal portion, which is secreted into the medium, and a cell-associated, highly O-glycosylated carboxyl-terminal portion (11,12,34,36,42,(52)(53)(54). Cleavage has been proposed to occur between residues 321 and 322 and between residues 342 and 343 (33,35).…”