Insertional activation of STAT3 and LCK by HIV-1 proviruses in T cell lymphomas

Retroviruses cause cancers in animals by integrating in or near oncogenes. Although HIV-1 infection increases the risk of cancer, most of the risk is associated with immunodeficiency and coinfection by oncogenic virus (Epstein-Barr virus, Kaposi sarcoma herpesvirus, and human papillomavirus). HIV-1 proviruses integrated in some oncogenes cause clonal expansion of infected T cells in vivo; however, the infected cells are not transformed, and it is generally believed that HIV-1 does not cause cancer directly. We show that HIV-1 proviruses integrated in the first introns of signal transducer and activator of transcription 3 (STAT3) and lymphocyte-specific protein tyrosine kinase (LCK) can play an important role in the development of T cell lymphomas. The development of these cancers appears to be a multistep process involving additional nonviral mutations, which could help explain why T cell lymphomas are rare in persons with HIV-1 infection.

Automated summary

HIV-1 infection increases cancer risk, mainly due to immunodeficiency and coinfection with oncogenic viruses. Proviruses integrated in genes like STAT3 and LCK can play a role in T cell lymphoma development. The development of these cancers involves additional nonviral mutations in a multistep process.