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Immunological and Molecular Virological Studies of Kaposi’s Sarcoma Patients with and Without HIV-1 Infection

Salum J Lidenge, University of Nebraska - Lincoln

Abstract

The African endemic Kaposi’s sarcoma (EnKS) is still prevalent in sub-Saharan Africa (SSA) despite high incidence of HIV-1 associated/epidemic Kaposi’s sarcoma (EpKS). While KSHV is clearly the etiologic agent of KS, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in KS remains unclear. The objective of this research was to investigate the role of HIV-1 in KS by comparative analysis of immune responses and transcriptome changes in EpKS and EnKS patients. Cytokines and antibody responses in circulation of EpKS and EnKS patients from Tanzania and Zambia were characterized. For the first time, we reported that EnKS patients mount high KSHV neutralizing antibody responses similar to EpKS patients and were higher than asymptomatic controls. Regulatory and anti-inflammatory cytokines (IL-10, IL-5, and TGF-β) were also elevated in EpKS and EnKS patients irrespective of HIV-1 co-infection. This suggested that in the circulation, KSHV induces B-cell instead of T-cell responses required to control KSHV infected and cancer cells. The lack of clear effects of HIV-1 on humoral responses of KS patients suggested that possibly HIV-1 exerts its effect locally at the site of the tumor. Therefore, we moved to investigate the impact of HIV-1 in KS tumors. Similarly, transcriptomes analysis revealed high concordance in gene expression profiles between EpKS and EnKS with undetectable or minimal HIV-1 transcripts in EpKS lesions. However, interferon related chemokines (CxCL-9, -10 and -11) were significantly upregulated in KS lesions compared to uninvolved control skins. Although, a T-cell chemoattractant CxCL-9 was demonstrated to be overexpressed at protein level in KS lesions compared to normal skin, there was poor immune cell infiltration and co-localization with KSHV infected cells in KS tumors independent of HIV-1 co-infection, suggesting a fundamental tumor immune evasion mechanism. Overall, the findings of this study suggest that KSHV drives KS pathogenesis while perhaps HIV-1 indirectly or systemically accelerates and exacerbates KSHV pathogenesis and KS development.

Subject Area

Virology|Immunology|Oncology

Recommended Citation

Lidenge, Salum J, "Immunological and Molecular Virological Studies of Kaposi’s Sarcoma Patients with and Without HIV-1 Infection" (2020). ETD collection for University of Nebraska - Lincoln. AAI28086339.
https://digitalcommons.unl.edu/dissertations/AAI28086339

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