Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA

• Published in: Nature communications Vol. 9; no. 1; pp. 4585 - 12
• Main Authors: Chen, Lechuang, Feng, Zhimin, Yue, Hong, Bazdar, Douglas, Mbonye, Uri, Zender, Chad, Harding, Clifford V., Bruggeman, Leslie, Karn, Jonathan, Sieg, Scott F., Wang, Bingcheng, Jin, Ge
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.11.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/95; 14/19; 38; 631/67; 631/67/1858; 692/4028/67/70; 96/1; 96/34; Acquired immune deficiency syndrome; AIDS; Antiretroviral agents; Antiretroviral therapy; Cancer; Cell activation; Cell proliferation; Epidermal growth factor; Epidermal growth factor receptors; Exosomes; Gene expression; Growth factors; Health risks; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Lung cancer; Lymphocytes; Lymphocytes T; multidisciplinary; Phosphorylation; Proto-oncogenes; Ribonucleic acid; RNA; Science; Science (multidisciplinary); TLR3 protein; Toll-like receptors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07006-2

People living with HIV/AIDS on antiretroviral therapy have increased risk of non-AIDS-defining cancers (NADCs). However, the underlying mechanism for development and progression of certain NADCs remains obscure. Here we show that exosomes released from HIV-infected T cells and those purified from blood of HIV-positive patients stimulate proliferation, migration and invasion of oral/oropharyngeal and lung cancer cells. The HIV transactivation response (TAR) element RNA in HIV-infected T-cell exosomes is responsible for promoting cancer cell proliferation and inducing expression of proto-oncogenes and Toll-like receptor 3 (TLR3)-inducible genes. These effects depend on the loop/bulge region of the molecule. HIV-infected T-cell exosomes rapidly enter recipient cells through epidermal growth factor receptor (EGFR) and stimulate ERK1/2 phosphorylation via the EGFR/TLR3 axis. Thus, our findings indicate that TAR RNA-containing exosomes from HIV-infected T cells promote growth and progression of particular NADCs through activation of the ERK cascade in an EGFR/TLR3-dependent manner. HIV patients have an increased risk of developing non-AIDS-defining cancers but the molecular mechanisms underlying this predisposition are unclear. Here the authors show that exosomes secreted by HIV-infected T cells or isolated from the blood of HIV-positive patients, stimulate oncogenic properties of cancer cells through the activation of ERK1/2 signaling pathway.