Tumor Virology

Investigators

Role of exosomes derived from HIV-infected T cells in progression of non-AIDS defining cancers and co-infection

Ge Jin, PhD

Certain viruses have been linked to an increased risk of certain types of cancer. This can occur through direct infection of cells, as well as through changes in the immune system and cellular processes caused by the virus. For example, people with HIV, who are often co-infected with viruses such as Kaposi sarcoma-associated herpesvirus (KSHV) and human papillomavirus (HPV), have a higher incidence rate of certain cancers, including head and neck and lung cancers. Additionally, the replication of HIV in T-cells can produce exosomes that can promote the proliferation and spread of oral and lung cancer cells. We have reported that exosomes released by HIV-infected T cells stimulate proliferation, migration, and invasion of cancer cells of the head and neck and lung.

Exosomes are small vesicles (membrane-bound particles) that are released by almost all types of cells and can be found in various body fluids, including blood plasma and saliva to mediate cell-cell communication and material transfer. HIV-associated exosomes interact with EGFR of cancer cells and promote the activation of MAPK/ERK signaling pathways, without activating EGFR. MAPK/ERK signaling pathways play a crucial role in regulating cellular processes such as cell division, migration, and survival. Thus, HIV-associated exosomes may promote proliferation and spread of cancer cells through activation of these pathways in an EGFR-dependent manner, a process can be blocked by Cetuxima, a monoclonal antibody to EGFR.

Additionally, HIV-associated exosomes enhance infectivity of KSHV in oral epithelial cells grown in monolayer culture or 3-dimentional organotypic culture platform. Exosomes produced by HIV-infected T cells contain HIV RNA and proteins. We have reported that the HIV transactivation response element (TAR) RNA, known to be required for the trans-activation of the viral promoter and for virus replication using the host transcription machinery, is the major cargo of HIV-associated exosomes to contribute to the tumor-promoting effects of these exosomes. EGFR blockade and inhibition of tyrosine kinases can eliminate the tumor-promoting effect of HIV-associated exosomes.

Selected Publications

Chen L, Feng Z, Yue H, Bazdar G, Mbonye U, Zender C, Harding CV, Bruggeman L, Karn J, Sieg SF, Wang B, Jin G (2018). Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA. Nat Commun. PMID: 30389917 PMCID: PMC6214989.

Chen L, Feng Z, Yuan G, Emerson CC, Stewart PL, Ye F, Jin G (2020). Human Immunodeficiency Virus-Associated Exosomes Promote Kaposi's Sarcoma-Associated Herpesvirus Infection via the Epidermal Growth Factor Receptor. J Virol. PMID: 32051269 PMCID: PMC7163124

Chen L, Chen R, Yao M, Feng Z, Yuan G, Ye F, Nguyen K, Karn J, McComsey GA, McIntyre TM, Jin G (2022). COVID-19 plasma exosomes promote proinflammatory immune responses in peripheral blood mononuclear cells. Sci Rep. PMID: 36526691 PMCID: PMC9756928.