Arachidonic Acid Derived Lipid Mediators Influence Kaposi's Sarcoma-Associated Herpesvirus Infection and Pathogenesis.

Jayashree A Chandrasekharan,Neelam Sharma-Walia

doi:10.3389/fmicb.2019.00358

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, particularly latent infection is often associated with inflammation. The arachidonic acid pathway, the home of several inflammation and resolution associated lipid mediators, is widely altered upon viral infections. Several in vitro studies show that these lipid mediators help in the progression of viral pathogenesis. This review summarizes the findings related to human herpesvirus KSHV infection and arachidonic acid pathway metabolites. KSHV infection has been shown to promote inflammation by upregulating cyclooxygenase-2 (COX-2), 5 lipoxygenase (5LO), and their respective metabolites prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) to promote latency and an inflammatory microenvironment. Interestingly, the anti-inflammatory lipid mediator lipoxin is downregulated during KSHV infection to facilitate infected cell survival. These studies aid in understanding the role of arachidonic acid pathway metabolites in the progression of viral infection, the host inflammatory response, and pathogenesis. With limited therapeutic options to treat KSHV infection, use of inhibitors to these inflammatory metabolites and their synthetic pathways or supplementing anti-inflammatory lipid mediators could be an effective alternative therapeutic.

Highlights

Kaposi’s sarcoma-associated herpesvirus or human herpesvirus 8 (HHV8) is the causative agent of KS, primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD), and KSHV inflammatory cytokine syndrome (KICS) (Cesarman and Knowles, 1999; Greene et al, 2007; Kalt et al, 2009; Ganem, 2010)
This review summarizes the key findings of the role of several enzymes and metabolites of the arachidonic acid pathway during KSHV infection
This study demonstrated that COX-2 and its metabolite prostaglandin E2 (PGE2) are upregulated during KSHV infection of primary endothelial cells; KSHV utilizes those to target several pathways that facilitate pathogenesis and angiogenesis (Sharma-Walia et al, 2010b)

Summary

Introduction

Kaposi’s sarcoma-associated herpesvirus or human herpesvirus 8 (HHV8) is the causative agent of KS, PEL, MCD, and KICS (Cesarman and Knowles, 1999; Greene et al, 2007; Kalt et al, 2009; Ganem, 2010). To validate the involvement of KSHV induced COX-2 on inflammatory cytokines and angiogenic factors, HMVEC-d cells were either pretreated with COX-2 inhibitors NS-398 or indomethacin or silenced for COX-2 gene expression (Sharma-Walia et al, 2010b). KSHV-induced COX-2 enhanced the levels of these molecules and promoted endothelial cell tube formation, while this effect was reversed upon blocking COX-2 using chemical inhibitors (Sharma-Walia et al, 2010b).

Results

Conclusion