Kaposi Sarcoma Herpes Virus Reprograms Mesenchymal Cell Glycosylation to control platelet-derived growth factor receptor A signaling

Authors

Tudela, J., Gutierrez, P., Montani, M., Bannoud, N., Garcia, P., Mariño, K., Abba, M., Cerliani, J., Naipauer, J., Lacunza, E., Mesri, E., Rabinovich, G., Croci, D.

Abstract

Kaposi sarcoma–associated herpesvirus (KSHV) reprograms host cellular pathways to promote viral persistence and tumor development by supporting the survival and expansion of infected and bystander cells. Among the signaling axes implicated in this process, oncogenic activation of receptor tyrosine kinases, particularly platelet-derived growth factor receptor alpha (PDGFRA), is a well-established hallmark of Kaposi sarcoma pathogenesis. However, the impact of virus-driven cell surface glycosylation changes in PDGFRA-associated signaling remains uncertain. Here, we identified a critical role for KSHV in reshaping the glycosylation landscape of mesenchymal stromal cells (MSCs), thereby reprogramming PDGFRA signaling. We show that KSHV infection enhances a unique glycan profile in human and mouse MSCs, enriched in branched complex N-glycans with limited α(2-6) sialylation, Transcriptomic analyses of KSHV-infected MSCs and Kaposi’s Sarcoma patient samples revealed a coordinated dysregulation of pathways involved in carbohydrate metabolism, nucleotide-sugar transport, and sialic acid turnover, with a particular focus on sialic acid turnover (NPL/NEU3), the UDP-N-acetylglucosamine transporters SLC35A3/B4, and complex N-glycan elongation (MGAT5/B3GNT2/B4GALT1) as critical nodes underlying reduced α(2-6) sialylation and increased N-glycan branching. This remodeled glycan landscape contributes to create a permissive context for galectin-1 (Gal-1) binding, which in turn enhances PDGFRA activation and downstream signaling. These findings identify an integral component of KSHV-driven mesenchymal cell reprogramming, unveiling a lectin-dependent mechanism of RTK activation in Kaposi sarcoma pathogenesis.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Jul 2026.

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