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Heterogeneity and Breadth of Host Antibody Response to KSHV Infection Demonstrated by Systematic Analysis of the KSHV Proteome


Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi sarcoma, primary effusion lymphoma and a form of multicentric Castleman's disease, affecting mainly persons with HIV, other immunosuppressed patients and elderly men. Such diseases are most common where KSHV prevalence is high, in sub-Saharan Africa and the Mediterranean, and amongst men who have sex with men. Various assays for the serodiagnosis of KSHV have been developed to investigate global KSHV epidemiology. ELISAs utilizing one lytic (K8.1) and one latent antigen (ORF73) are often used. However, a more complete characterization of immune responses to all KSHV antigens may have important epidemiologic and clinical applications. We systematically expressed and purified 73 of the 85 proteins encoded by KSHV and analysed serologic responses in patients with KSHV-associated malignancies compared to healthy subjects. We identified significant reactivity to ORF38, ORF61, ORF59 and K5, in addition to the known K8.1, ORF73 and ORF65. Reactivity patterns were varied; however, HIV infected individuals were reactive to more antigens, with greater intensity. Next, we developed a bead-based assay that can test a small sample simultaneously for six KSHV antigens. The new tool can improve the detection of KSHV and the characterization of asymptomatic infection and KSHV associated diseases.


Vyšlo v časopise: Heterogeneity and Breadth of Host Antibody Response to KSHV Infection Demonstrated by Systematic Analysis of the KSHV Proteome. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004046
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004046

Souhrn

Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi sarcoma, primary effusion lymphoma and a form of multicentric Castleman's disease, affecting mainly persons with HIV, other immunosuppressed patients and elderly men. Such diseases are most common where KSHV prevalence is high, in sub-Saharan Africa and the Mediterranean, and amongst men who have sex with men. Various assays for the serodiagnosis of KSHV have been developed to investigate global KSHV epidemiology. ELISAs utilizing one lytic (K8.1) and one latent antigen (ORF73) are often used. However, a more complete characterization of immune responses to all KSHV antigens may have important epidemiologic and clinical applications. We systematically expressed and purified 73 of the 85 proteins encoded by KSHV and analysed serologic responses in patients with KSHV-associated malignancies compared to healthy subjects. We identified significant reactivity to ORF38, ORF61, ORF59 and K5, in addition to the known K8.1, ORF73 and ORF65. Reactivity patterns were varied; however, HIV infected individuals were reactive to more antigens, with greater intensity. Next, we developed a bead-based assay that can test a small sample simultaneously for six KSHV antigens. The new tool can improve the detection of KSHV and the characterization of asymptomatic infection and KSHV associated diseases.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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