Immunodominant 'Asymptomatic' Herpes Simplex Virus 1 and 2 Protein Antigens Identified by Probing Whole-ORFome Microarrays with Serum Antibodies from Seropositive Asymptomatic versus Symptomatic Individuals
| Autor: | Lbachir BenMohamed, Philip L. Felgner, Mina Kalantari, D. Huw Davies, Sookhee Chun, Chang Hyun Lim, Gargi Dasgupta, Payam Falatoonzadeh, Aziz Alami Chentoufi |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Adolescent Proteome viruses Herpesvirus 2 Human Immunology Protein Array Analysis Immunodominance Herpesvirus 1 Human medicine.disease_cause Antibodies Viral Microbiology Asymptomatic Herpesviridae Virus Serology Open Reading Frames Young Adult Antigen Seroepidemiologic Studies Virology Medicine and Health Sciences medicine Cluster Analysis Humans Serologic Tests Antigens Viral biology Immunodominant Epitopes Herpes Simplex Middle Aged Herpes simplex virus Insect Science biology.protein Pathogenesis and Immunity Female medicine.symptom Antibody |
| Zdroj: | Dasgupta, Gargi; Chentoufi, Aziz A.; Kalantari, Mina; Falatoonzadeh, Payam; Chun, Sookhee; Lim, Chang Hyun; et al.(2012). Immunodominant "Asymptomatic" Herpes Simplex Virus 1 and 2 Protein Antigens Identified by Probing Whole-ORFome Microarrays with Serum Antibodies from Seropositive Asymptomatic versus Symptomatic Individuals. Journal of Virology, 86(8), 4358-4369. UC Irvine: Institute for Clinical and Translational Science. Retrieved from: http://www.escholarship.org/uc/item/8r55z1zq |
| Popis: | Herpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 and HSV-2 immunodominant “asymptomatic” antigens (ID-A-Ags), which are strongly recognized by B and T cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic HSV vaccine. In contrast, immunodominant “symptomatic” antigens (ID-S-Ags) may exacerbate herpetic disease and therefore must be excluded from any HSV vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames(ORFs) (ORFomes) were constructed and probed with sera from 32 HSV-1-, 6 HSV-2-, and 5 HSV-1/HSV-2-seropositive individuals and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic ( n = 10) and asymptomatic ( n = 10) individuals. We found that (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1- and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV-1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from seropositive individuals; and (iv) interestingly, four HSV-1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients ( P < 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag ( P < 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient “asymptomatic” vaccine against ocular, orofacial, and genital herpes. |
| Databáze: | OpenAIRE |
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