The Kaposi's Sarcoma-Associated Herpesvirus (KSHV) gH/gL Complex Is the Predominant Neutralizing Antigenic Determinant in KSHV-Infected Individuals.

Yasaman Mortazavi,John T West,Salum J Lidenge,For Yue Tso,Tara Tran,Charles Wood

doi:10.3390/v12030256

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that plasma from a majority of KSHV neutralizers recognizes multiple viral glycoproteins. Moreover, the breadth of nAbs responses against these viral glycoproteins varies among endemic KS, epidemic KS and asymptomatic KSHV-infected individuals. Importantly, among the KSHV glycoproteins, the gH/gL complex, but neither gH nor gL alone, showed the highest adsorption of KSHV-specific nAbs. This activity was detected in 80% of the KSHV-infected individuals regardless of their KS status. The findings suggest that the gH/gL complex is the predominant antigenic determinant of KSHV-specific nAbs. Therefore, gH/gL is a potential target for development of KSHV prophylactic vaccines.

Highlights

Kaposi’s sarcoma-associated herpesvirus (KSHV), known as human herpesvirus-8 (HHV-8), is the causative agent of all forms of Kaposi sarcoma (KS) and two additional lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD) [1,2].The distribution of KSHV varies globally
We studied the ability of various KSHV glycoproteins in the adsorption/removal of KSHV-specific neutralizing antibodies (nAbs) from the plasma of KSHV-infected individuals who have high nAbs titers
The results reveal that the gH/gL complex depleted the highest amount of KSHV-specific nAbs in the majority of KSHV-infected individuals, suggesting that gH/gL is the most prominent target of KSHV-specific nAbs, and the most plausible antigenic target for prophylactic vaccine development against KSHV

Summary

Introduction

Kaposi’s sarcoma-associated herpesvirus (KSHV), known as human herpesvirus-8 (HHV-8), is the causative agent of all forms of Kaposi sarcoma (KS) and two additional lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD) [1,2]. In some areas such as sub-Saharan Africa (SSA), KSHV seroprevalence can be as high as 80%, whereas in the US and Europe, the prevalence is. The prevalence of KS increases significantly with HIV-1 infection, making it one of the leading cancers among people living with HIV/AIDS in SSA [5,6]. 44,000 new cases of KS emerge annually, with the highest incidence occurring in Africa, where KSHV is endemic [7]. The two main clinical manifestations of KS are Endemic KS (EnKS) and Epidemic

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Conclusion