A natural HIV p17 protein variant up-regulates the LMP-1 EBV oncoprotein and promotes the growth of EBV-infected B-lymphocytes: implications for EBV-driven lymphomagenesis in the HIV setting

Martorelli, Debora, Muraro, Elena, Mastorci, Katy, Dal Col, Jessica, Fae, Damiana Antonia, Furlan, Chiara, Giagulli, Cinzia, Caccuri, Francesca, Rusnati, Marco, Fiorentini, Simona, Carbone, Antonino, Caruso, Arnaldo and Dolcetti, Riccardo (2015) A natural HIV p17 protein variant up-regulates the LMP-1 EBV oncoprotein and promotes the growth of EBV-infected B-lymphocytes: implications for EBV-driven lymphomagenesis in the HIV setting. International Journal of Cancer, 137 6: 1374-1385. doi:10.1002/ijc.29494


Author Martorelli, Debora
Muraro, Elena
Mastorci, Katy
Dal Col, Jessica
Fae, Damiana Antonia
Furlan, Chiara
Giagulli, Cinzia
Caccuri, Francesca
Rusnati, Marco
Fiorentini, Simona
Carbone, Antonino
Caruso, Arnaldo
Dolcetti, Riccardo
Title A natural HIV p17 protein variant up-regulates the LMP-1 EBV oncoprotein and promotes the growth of EBV-infected B-lymphocytes: implications for EBV-driven lymphomagenesis in the HIV setting
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 1097-0215
0020-7136
Publication date 2015-09-15
Year available 2015
Sub-type Article (original research)
DOI 10.1002/ijc.29494
Open Access Status Not Open Access
Volume 137
Issue 6
Start page 1374
End page 1385
Total pages 12
Place of publication Hoboken NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
Human immunodeficiency virus p17 matrix protein is released by infected cells and may accumulate within lymphoid tissues where it may deregulate the biological activities of different cell populations by binding to CXCR1 and CXCR2 cellular receptors. S75X, a natural p17 variant, was recently shown to enhance the malignant properties of lymphoma cells. We investigated a reference p17 protein and the S75X variant for their ability to bind to Epstein–Barr virus (EBV)-infected primary and fully transformed B-lymphocytes and trigger downstream effects of potential pathogenic relevance. We demonstrate that EBV infection of primary B-lymphocytes or the ectopic expression of the latent membrane protein-1 viral oncoprotein in EBV-negative B-cells up-regulates CXCR2, but not CXCR1. Multispectral imaging flow cytometry showed that EBV-infected primary B-cells more efficiently bind and internalize p17 proteins as compared with activated B-lymphocytes. The S75X variant bound more efficiently to EBV-infected primary and fully transformed B-lymphocytes compared with reference p17, because of a higher affinity to CXCR2, and enhanced the proliferation of these cells, an effect associated with cyclin D2 and D3 up-regulation and increased interleukin-6 production. Notably, the S75X variant markedly up-regulated latent membrane protein-1 expression at both mRNA and protein levels and enhanced the activation of Akt, ERK1/2 and STAT3 signaling, thereby contributing to EBV+ B-cell growth promotion. These results indicate that EBV infection sensitizes B-lymphocytes to CXCR2-mediated effects of p17 proteins and provide evidence supporting a possible contribution of natural p17 variants to EBV-driven lymphomagenesis in the human immunodeficiency virus setting.
Keyword Epstein-Barr virus
Lymphoma
HIV p17
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
 
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