Suppression of DC-SIGN and gH Reveals Complex, Subset-Specific Mechanisms for KSHV Entry in Primary B Lymphocytes

• Published in: Viruses Vol. 13; no. 8; p. 1512
• Main Authors: Palmerin, Nancy, Aalam, Farizeh, Nabiee, Romina, Muniraju, Murali, Ogembo, Javier Gordon, Totonchy, Jennifer
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.07.2021; MDPI
• Subjects: B-Lymphocytes - immunology; B-Lymphocytes - virology; Blood; Capsid Proteins - genetics; Cell Adhesion Molecules - genetics; Cells, Cultured; DC-SIGN; DC-SIGN protein; Dendritic cells; Dengue fever; Fibroblasts; Flow cytometry; Genomes; Glycoprotein H; Glycoproteins; Herpesvirus 8, Human - genetics; Herpesvirus 8, Human - immunology; Host Microbial Interactions - genetics; Host Microbial Interactions - immunology; Humans; Immune system; Immunocompromised hosts; Immunoproliferative diseases; Infections; KSHV; Lectins, C-Type - genetics; Lymphocytes; Lymphocytes B; lymphotropism; Palatine Tonsil - cytology; Palatine Tonsil - immunology; Receptors, Cell Surface - genetics; Sarcoma; Tonsil; viral entry; Virus Internalization; Viruses; viral entry; glycoprotein H; KSHV; DC-SIGN; lymphotropism
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13081512

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of multiple cancers in immunocompromised patients including two lymphoproliferative disorders associated with KSHV infection of B lymphocytes. Despite many years of research into the pathogenesis of KSHV associated diseases, basic questions related to KSHV molecular virology remain unresolved. One such unresolved question is the cellular receptors and viral glycoproteins needed for KSHV entry into primary B lymphocytes. In this study, we assess the contributions of KSHV glycoprotein H (gH) and the cellular receptor DC-SIGN to KSHV infection in tonsil-derived B lymphocytes. Our results show that (1) neither KSHV-gH nor DC-SIGN are essential for entry into any B cell subset, (2) DC-SIGN does play a role in KSHV entry into tonsil-derived B cells, but in all B cell subtypes alternative entry mechanisms exist, (3) KSHV-gH can participate in KSHV entry into centrocytes via a DC-SIGN independent entry mechanism, and (4) in the absence of KSHV-gH, DC-SIGN is required for KSHV entry into centrocytes. Our results provide a first glimpse into the complexity of KSHV entry in the lymphocyte compartment and highlight that multiple subset-dependent entry mechanisms are employed by KSHV which depend upon multiple cellular receptors and multiple KSHV glycoproteins.