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

Lechuang Chen, Zhimin Feng, Hong Yue, Douglas Bazdar, Uri Mbonye, Chad Zender, Clifford V. Harding, Leslie Bruggeman, Jonathan Karn, Scott F. Sieg, Bingcheng Wang and Ge Jin ()
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Lechuang Chen: Case Western Reserve University School of Dental Medicine
Zhimin Feng: Case Western Reserve University School of Dental Medicine
Hong Yue: Case Western Reserve University School of Dental Medicine
Douglas Bazdar: Case Western Reserve University School of Medicine
Uri Mbonye: Case Western Reserve University School of Medicine
Chad Zender: Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center
Clifford V. Harding: Case Western Reserve University
Leslie Bruggeman: Case Western Reserve University and University Hospitals of Cleveland
Jonathan Karn: Case Western Reserve University School of Medicine
Scott F. Sieg: Case Western Reserve University School of Medicine
Bingcheng Wang: Case Western Reserve University
Ge Jin: Case Western Reserve University School of Dental Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07006-2

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