Simian immunodeficiency virus and human immunodeficiency virus type 1 matrix proteins specify different capabilities to modulate b cell growth

Francesca Caccuri, Cinzia Giagulli, Joachim Reichelt, Debora Martorelli, Stefania Marsico, Antonella Bugatti, Ines Barone, Marco Rusnati, Carlos A. Guzman, Riccardo Dolcetti, Arnaldo Caruso

Research output: Contribution to journalArticlepeer-review

Abstract

Exogenous HIV-1 matrix protein p17 (p17) deregulates the function of different cells after its N-terminal loop (AT20) binding to the chemokine receptors CXCR1 and CXCR2. One site within AT20 has been recently found to be the major determinant of viral fitness following transmission of simian immunodeficiency virus (SIV) to the human host. Therefore, we sought to determine whether SIV matrix protein (MA) was already capable of interacting with CXCR1 and CXCR2 and mimic p17 biological activities rather than this being a newly acquired function during host adaptation. We show here that SIV MA binds with the same affinity of p17 to CXCR1 and CXCR2 and displays both p17 proangiogenic on human primary endothelial cells and chemotactic activity on human primary monocytes and B cells. However, SIV MA exhibited a higher degree of plasticity than p17 in the C terminus, a region known to play a role in modulating B cell growth. Indeed, in contrast to p17, SIV MA was found to activate the phosphatidylinositol 3-kinase/Akt signaling pathway and strongly promote B cell proliferation and clonogenic activity. Interestingly, we have recently highlighted the existence of a Ugandan HIV-1 strain-derived p17 variant (S75X) with the same B cell growth-promoting activity of SIV MA. Computational modeling allowed us to hypothesize an altered C terminus/core region interaction behind SIV MA and S75X activity. Our findings suggest the appearance of a structural constraint in the p17 C terminus that controls B cell growth, which may help to elucidate the evolutionary trajectory of HIV-1.

Original languageEnglish
Pages (from-to)5706-5717
Number of pages12
JournalJournal of Virology
Volume88
Issue number10
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Immunology
  • Virology

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