Lymphomagenic properties of a HIV p17 variant derived from a splenic marginal zone lymphoma occurred in a HIV-infected patient: Hematological Oncology

Francesca Caccuri, Elena Muraro, Annunziata Gloghini, Ombretta Turriziani, Mara Riminucci, Cinzia Giagulli, Katy Mastorci, Damiana Antonia Fae', Simona Fiorentini, Antonino Caruso, Arnaldo Carbone, Riccardo Dolcetti

Research output: Contribution to journalArticle

Abstract

Despite antiretroviral therapy, HIV+ individuals still have increased risk to develop lymphomas, including marginal zone lymphomas, suggesting that factors other than HIV-related immunosuppression are probably acting as lymphomagenic factors in the HIV setting. The possible pathogenic involvement of HIV p17 protein variants was investigated in a particularly informative case of HIV-related splenic marginal zone lymphoma, which was negative for oncogenic virus infections, thus allowing us to assess the possible direct contribution of these HIV-encoded proteins to lymphomagenesis. The presence of p17 protein was analyzed by immunohistochemistry in lymphoma tissue. Recombinant p17 protein derived from the dominant sequence detected in plasma and lymphoma biopsy was characterized for B-cell proliferation, clonogenicity in soft agar, in vitro tube formation and wound healing. Intracellular signaling was investigated by immunoblotting. HIV p17 protein was detected in reactive lymphoid follicles but not within lymphoma cells. An identical dominant variant p17 sequence, p17-Lyrm, carrying a 117 to 118 Ala-Ala insertion was detected in both plasma and lymphoma tissue. Recombinant p17-Lyrm enhanced B-cell proliferation and clonogenicity promoted the formation of capillary-like structures and enhanced endothelial cell migration. Unlike reference p17, the p17-Lyrm variant enhanced the activation of Akt and ERK, critical kinases in lymphomagenesis. p17-Lyrm clonogenic activity was dependent on the activation of Akt but not of ERK1/2. These results indicated that HIV p17 variants with distinct molecular signatures and functional properties may accumulate in lymphoid tissues of HIV-infected individuals where they may act as a local stimulus promoting the development of lymphomas.
Original languageEnglish
Pages (from-to)176-184
Number of pages9
JournalHematological Oncology
Volume37
Issue number2
DOIs
Publication statusPublished - 2019

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Keywords

  • Female
  • Humans
  • Middle Aged
  • HIV-1
  • HIV Infections
  • HIV
  • Mutagenesis, Insertional
  • Neoplasm Proteins
  • Lymphoma, B-Cell, Marginal Zone
  • Splenic Neoplasms
  • B lymphocytes
  • Cell Transformation, Viral
  • gag Gene Products, Human Immunodeficiency Virus
  • HIV Antigens
  • lymphomagenesis
  • marginal zone lymphoma
  • p17

Cite this

Caccuri, F., Muraro, E., Gloghini, A., Turriziani, O., Riminucci, M., Giagulli, C., Mastorci, K., Fae', D. A., Fiorentini, S., Caruso, A., Carbone, A., & Dolcetti, R. (2019). Lymphomagenic properties of a HIV p17 variant derived from a splenic marginal zone lymphoma occurred in a HIV-infected patient: Hematological Oncology. Hematological Oncology, 37(2), 176-184. https://doi.org/10.1002/hon.2562