Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17

• DOI: 10.1038/srep38027
• Publication Date: 2016-12-01T10:47:07Z
• Authors: Francesca Caccuri; Maria Luisa Iaria; Federica Campilongo; Kristen Varney; Alessandro Rossi; Stefania Mitola; Silvia Schiarea; Antonella Bugatti; Pietro Mazzuca; Cinzia Giagulli; Simona Fiorentini; Wuyuan Lu; Mario Salmona; Arnaldo Caruso
• Keywords: Proteolysis

Abstract The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood different organs tissues even HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, deregulates the function involved AIDS pathogenesis. mechanism secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that can produce Gag without spreading infection model viral latency. Here we show -expressing cells, secretion biologically active takes place at plasma membrane occurs following its interaction with phosphatidylinositol-(4,5)-bisphosphate subsequent cleavage from precursor (Pr55 ) operated cellular aspartyl proteases. These enzymes operate more complex polypeptide proteolysis than protease, thus hypothetically generating slightly truncated or elongated p17s their C-terminus. 17 C-terminal residues excised was found structurally functionally identical full-length demonstrating final region irrelevant for protein’s biological activity. findings offer new opportunities identify treatment strategies inhibiting release extracellular microenvironment.