CD40 Upregulation is Independent of HHV-8 in the Pathogenesis of Kaposi's Sarcoma
Overview
Affiliations
Aims: Human herpesvirus 8 (HHV-8) is now acknowledged as the infective cofactor in the pathogenesis of Kaposi's sarcoma. The mode by which HHV-8 causes Kaposi's sarcoma is unresolved and it is probable that it acts in conjunction with other factors including cytokines, anti-apoptosis proteins, and cell surface receptors. CD40, a cell membrane receptor belonging to the tumour necrosis factor receptor super family, promotes B cell survival and is expressed constitutively on endothelial cells. It is upregulated on cytokine treatment and has been documented recently in Kaposi's sarcoma. Because the HHV-8 genome contains cytokine homologues, this study investigated whether CD40 expression in Kaposi's sarcoma correlated with HHV-8 status, using a unique set of HHV-8 positive and negative specimens.
Methods: Twenty one paraffin wax embedded samples of Kaposi's sarcoma were selected, of which 18 were screened for the presence of HHV-8 using both conventional solution phase and TaqMan polymerase chain reaction (PCR). CD40 immunohistochemistry was assessed using a biotinylated amplification system. Staining was scored semiquantitatively.
Results: The results indicated that the expression of CD40 is independent of viral status, being present in both HHV-8 positive and negative specimens.
Conclusions: This suggests that HHV-8 promotes Kaposi's sarcoma cell survival following infection by mechanisms other than those involving CD40.
Real-time Fluorescent PCR Techniques to Study Microbial-Host Interactions.
Mackay I, Arden K, Nitsche A Methods Microbiol. 2024; 34:255-330.
PMID: 38620210 PMC: 7148886. DOI: 10.1016/S0580-9517(04)34010-9.
Rijs Z, Shifai A, Bosma S, Kuppen P, Vahrmeijer A, Keereweer S Cancers (Basel). 2021; 13(3).
PMID: 33535618 PMC: 7867119. DOI: 10.3390/cancers13030557.
Mackay I, Arden K, Nitsche A Nucleic Acids Res. 2002; 30(6):1292-305.
PMID: 11884626 PMC: 101343. DOI: 10.1093/nar/30.6.1292.