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Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
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 and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency. Here we show that in Gag-expressing cells, secretion of biologically active p17 takes place at the plasma membrane and occurs following its interaction with phosphatidylinositol-(4,5)-bisphosphate and its subsequent cleavage from the precursor Gag (Pr55Gag) operated by cellular aspartyl proteases. These enzymes operate a more complex Gag polypeptide proteolysis than the HIV-1 protease, thus hypothetically generating slightly truncated or elongated p17s in their C-terminus. A 17 C-terminal residues excised p17 was found to be structurally and functionally identical to the full-length p17 demonstrating that the final C-terminal region of p17 is irrelevant for the protein’s biological activity. These findings offer new opportunities to identify treatment strategies for inhibiting p17 release in the extracellular microenvironment.
- Subjects :
- 0301 basic medicine
Signal peptide
Phosphatidylinositol 4,5-Diphosphate
Proteases
Aspartic Acid Proteases
HIV Antigens
medicine.medical_treatment
Proteolysis
viruses
HIV Infections
Biology
gag Gene Products, Human Immunodeficiency Virus
Article
03 medical and health sciences
Jurkat Cells
0302 clinical medicine
immune system diseases
Virus latency
Retroviral aspartyl protease
medicine
Humans
Secretion
Protein Precursors
Protease
Viral matrix protein
Multidisciplinary
medicine.diagnostic_test
Cell Membrane
virus diseases
medicine.disease
Cell biology
Virus Latency
030104 developmental biology
Biochemistry
030220 oncology & carcinogenesis
HIV-1
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....f6b88fbeadd63849a29fb46ee39bd833
- Full Text :
- https://doi.org/10.1038/srep38027