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

Date Published: March 27, 2014

Publisher: Public Library of Science

Author(s): Nazzarena Labo, Wendell Miley, Vickie Marshall, William Gillette, Dominic Esposito, Matthew Bess, Alexandra Turano, Thomas Uldrick, Mark N. Polizzotto, Kathleen M. Wyvill, Rachel Bagni, Robert Yarchoan, Denise Whitby, Dirk P. Dittmer.


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.

Partial Text

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), primary effusion lymphoma (PEL) and a type of multicentric Castleman’s disease (MCD) [1]–[3]. Unlike other human herpesviruses, KSHV is not ubiquitous in human populations. The prevalence of KSHV infection generally parallels the incidence of KS, and varies strikingly according to geography, ethnicity, and certain behavioral risk factors [4]. Prevalence is very high in sub-Saharan Africa, ranging from 35 to 60% [4]–[7] and elevated in Mediterranean regions, from 10 to 30% [8], [9]. In South America, prevalence is high in Amerindians but not in non-Amerindians living in adjoining areas in comparable conditions [10], [11]. In the US and Western Europe, prevalence is generally low but is elevated in men who have sex with men (MSM) [12], [13] and in those born in certain areas of elevated KSHV prevalence [14].

In order to systematically evaluate the antigenic characteristics of KSHV-encoded proteins, we sought to express the entire KSHV proteome. We obtained recombinant proteins from 72 of the more than 85 described ORFs. The K1 and K15 genes were excluded from this study because of their high variability. Expression and/or purification of the few remaining proteins were not possible due to various technical issues.




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