Co-Infection and Cancer: Host-Pathogen Interaction between Dendritic Cells and HIV-1, HTLV-1, and Other Oncogenic Viruses

Dendritic cells (DCs) function as a link between innate and adaptive immune responses. Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to propagate infection. Coinfection of HTLV-1 and HIV-1 has implications for cancer malignancies. Both viruses initially infect DCs and propagate the infection to CD4(+) T cells through cell-to-cell transmission using mechanisms including the formation of virologic synapses, viral biofilms, and conduits. These retroviruses are both neurotrophic with neurovirulence determinants. The neuropathogenesis of HIV-1 and HTLV-1 results in neurodegenerative diseases such as HIV-associated neurocognitive disorders (HAND) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Infected DCs are known to traffic to the brain (CNS) and periphery (PNS, lymphatics) to induce neurodegeneration in HAND and HAM/TSP patients. Elevated levels of neuroinflammation have been correlated with cognitive decline and impairment of motor control performance. Current vaccinations and therapeutics for HIV-1 and HTLV-1 are assessed and can be applied to patients with HIV-1-associated cancers and adult T cell leukemia/lymphoma (ATL). These diseases caused by co-infections can result in both neurodegeneration and cancer. There are associations with cancer malignancies and HIV-1 and HTLV-1 as well as other human oncogenic viruses (EBV, HBV, HCV, HDV, and HPV). This review contains current knowledge on DC sensing of HIV-1 and HTLV-1 including DC-SIGN, Tat, Tax, and current viral therapies. An overview of DC interaction with oncogenic viruses including EBV, Hepatitis viruses, and HPV is also provided. Vaccines and therapeutics targeting host-pathogen interactions can provide a solution to co-infections, neurodegeneration, and cancer.

Automated summary

Dendritic cells play a crucial role in the infections of HIV-1 and HTLV-1 and are associated with neurodegenerative diseases and cancer. Infected dendritic cells can transmit the infection to other cells and contribute to the development of neurodegenerative diseases. Current vaccines and therapies targeting host-pathogen interactions can be applied to patients with these diseases.