Insights Into Kaposi Sarcoma-Associated Herpesvirus-Specific Humoral Responses

Abstract

Kaposi sarcoma (KS) remains a global health concern. In sub-Saharan Africa, where there is a high burden of HIV-1 infection, there is also a high prevalence of infection by the etiologic agent of KS, the KS-associated herpesvirus (KSHV). Despite the successes of antiretroviral treatment (ART), the burden of KS and other KSHV-associated malignancies among people living with HIV under ART remained high, stressing the need for a greater understanding of the immune response against KSHV infection. Here, we review the current information on KSHV-specific humoral response in infected individuals in detail. We discuss the significance of anti-KSHV responses, mechanisms used by KSHV to subvert and modulate humoral immunity, and implications for pathogenesis and therapy. We highlight cutting-edge serological assays and bioinformatics tools that aid the development of effective vaccines against KSHV, underscoring the complexity of the humoral response and its critical role within the context of infection and vaccine design.

Keywords: KSHV; humoral immunity; immunoinformatics; serology; vaccine development.

FIGURE 1 ∣

Illustrative overview of the serological tools used to characterize KSHV-specific Ab responses. (A) Immunofluorescence assay (IFA) detects KSHV using fluorophore-tagged conjugated Abs. (B) Enzyme-linked immunosorbent assay (ELISA) involves antigen-coated plates and colorimetric detection of bound KSHV Abs via enzyme-conjugated secondary Abs. (C) Luminex-based multiplex bead assay utilizes antigen-coated beads to detect KSHV antibodies with high-throughput flow cytometry readout, while (D) Luciferase Immunoprecipitation System (LIPS) uses luciferase-tagged antigens incubated with patient sera and protein A/G beads, which are quantified via luminescence. (E) A protein microarray involves expressing and purifying KSHV open reading frames (ORFs), printed on slides and incubating with sera for proteome-scale Ab profiling. (F) Phage immunoprecipitation and sequencing (PhIP-seq) screens patient plasma against an extensive overlapping viral peptide library (VirScan). This is followed by magnetic pull-down of Ag: Ab complexes and multiplexed next-generation sequencing to profile viral Ab repertoires.