title: Heterogeneity and breadth of host antibody response to KSHV infection demonstrated by systematic analysis of the KSHV proteome.
abstract: The Kaposi sarcoma associated herpesvirus (KSHV) genome encodes more than 85 open reading frames (ORFs). Serological evaluation of KSHV infection now generally relies on reactivity to just one latent and/or one lytic protein (commonly ORF73 and K8.1). Most of the other polypeptides encoded by the virus have unknown antigenic profiles. We have systematically expressed and purified products from 72 KSHV ORFs in recombinant systems and analyzed seroreactivity in US patients with KSHV-associated malignancies, and US blood donors (low KSHV seroprevalence population). We identified several KSHV proteins (ORF38, ORF61, ORF59 and K5) that elicited significant responses in individuals with KSHV-associated diseases. In these patients, patterns of reactivity were heterogeneous; however, HIV infection appeared to be associated with breadth and intensity of serological responses. Improved antigenic characterization of additional ORFs may increase the sensitivity of serologic assays, lead to more rapid progresses in understanding immune responses to KSHV, and allow for better comprehension of the natural history of KSHV infection. To this end, we have developed a bead-based multiplex assay detecting antibodies to six KSHV antigens.
authors.affiliation: Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Labo
authors.affiliation: Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Wendell
authors.initials: W
authors.lastname: Miley
authors.affiliation: Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Vickie
authors.initials: V
authors.lastname: Marshall
authors.affiliation: Protein Expression Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Gillette
authors.affiliation: Protein Expression Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Dominic
authors.initials: D
authors.lastname: Esposito
authors.affiliation: Protein Expression Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bess
authors.affiliation: Protein Expression Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Turano
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Uldrick
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Polizzotto
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wyvill
authors.affiliation: Protein Expression Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bagni
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
authors.affiliation: Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D060085:Coinfection / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007158:Immunologic Techniques; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames / Q000235:genetics; D020543:Proteome / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D020543:Proteome