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

Nat Commun. 2018 Nov 2;9(1):4585. doi: 10.1038/s41467-018-07006-2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression*
  • ErbB Receptors / metabolism
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Gene Expression Regulation
  • HEK293 Cells
  • HIV Infections / blood
  • HIV Infections / metabolism*
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / physiology*
  • Humans
  • MAP Kinase Signaling System
  • Mice, Nude
  • Neoplasms / pathology*
  • Phosphorylation
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Toll-Like Receptor 3 / metabolism

Substances

  • Toll-Like Receptor 3
  • ErbB Receptors