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.

中文翻译：

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源自HIV-1感染细胞的外泌体通过HIV TAR RNA促进癌症的生长和进展。

接受抗逆转录病毒疗法治疗的艾滋病毒/艾滋病患者增加了非艾滋病定义的癌症（NADC）的风险。但是，某些NADC的发展和进步的基本机制仍然不清楚。在这里，我们显示从HIV感染的T细胞释放的外泌体和从HIV阳性患者血液中纯化的外泌体刺激口腔/口咽和肺癌细胞的增殖，迁移和侵袭。HIV感染的T细胞外来体中的HIV反式激活反应（TAR）元素RNA负责促进癌细胞的增殖并诱导原癌基因和Toll样受体3（TLR3）诱导型基因的表达。这些作用取决于分子的环/凸出区域。被HIV感染的T细胞外泌体通过表皮生长因子受体（EGFR）迅速进入受体细胞，并通过EGFR / TLR3轴刺激ERK1 / 2磷酸化。因此，我们的发现表明来自HIV感染的T细胞的含TAR RNA的外泌体通过以EGFR / TLR3依赖性方式激活ERK级联来促进特定NADC的生长和进程。