Simplex Virus 1 and 2 by

Routine serodiagnosis of herpes simplex virus (HSV) infections is currently performed using recombinant glycoprotein G (gG) antigens from herpes simplex virus 1 (HSV-1) and HSV-2. This is a single-antigen test and has only one diagnostic application. Relatively little is known about HSV antigenicity at the proteome-wide level, and the full potential of mining the antibody reper-toire to identify antigens with other useful diagnostic properties and candidate vaccine antigens is yet to be realized. To this end we produced HSV-1 and-2 proteomemicroarrays in Escherichia coli and probed them against a panel of sera from patients sero-typed using commercial gG-1 and gG-2 (gGs for HSV-1 and-2, respectively) enzyme-linked immunosorbent assays. We identi-fied many reactive antigens in both HSV-1 and-2, some of which were type specific (i.e., recognized by HSV-1- or HSV-2-positive donors only) and others of which were nonspecific or cross-reactive (i.e., recognized by both HSV-1- and HSV-2-positive do-nors). Both membrane and nonmembrane virion proteins were antigenic, although type-specific antigens were enriched for membrane proteins, despite being expressed in E. coli. Herpes simplex virus 1 (HSV-1) and HSV-2 cause significanthuman morbidity. HSV-2 is the causative agent of most re-current genital herpes lesions and is sexually transmitted. Infec-tions are often asymptomatic, and most infected individuals are unaware of the infection, yet HSV-2 is associated with an in-creased risk of HIV acquisition (33) and an increased risk durin