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

Abstract

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.

Use of Hu-PBL Mice to Study Pathogenesis of Human-Restricted Viruses

“…A third interesting approach that could be developed in PBL models is the studying of viral coinfections, which can arise in humans as a result of acute or chronic infections, such as those caused by HIV and other viruses [ 142 , 143 , 144 ], CMV and HBV [ 145 ], or SARS-CoV-2 and influenza viruses [ 146 , 147 ]. It would be attractive to learn how a past infection may influence the outcome of a subsequent one with a different virus, or vice versa, to develop better therapeutical approaches for those patients.…”

HPV co‐infections with other pathogens in cancer development: A comprehensive review

“…In co‐infection, pathogens can interact either directly with one another or indirectly through the host's resources or immune system. These interactions within co‐infected hosts change the transmission, clinical progression and control of multiple infectious diseases compared to single pathogen infections 76,77 . HPV infection (a main risk factor for human malignancies) often increases the risk of co‐infection with other infectious agents such as viruses and bacteria 74 .…”

“…These interactions within co-infected hosts change the transmission, clinical progression and control of multiple infectious diseases compared to single pathogen infections. 76,77 HPV infection (a main risk factor for human malignancies) often increases the risk of co-infection with other infectious agents such as viruses and bacteria. 74 A brief discussion of these co-infections is described in the next sections.…”

Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review

“…HIV mainly infects the CD4 receptor, whereas HTLV interacts with glucose transporter 1, neuropilin-1, and heparan sulfate proteoglycans to enter target cells. In addition to CD4+ T cells, both HIV and HTLV-1 infect non-lymphoid monocytic cells, such as macrophages and dendritic cells; however, both cause diseases originating from CD4+ helper T cells [16]. During HIV infection, direct cell destruction because of HIV infection and proliferation and destruction of infected cells by HIV antigen-specific CD8+ cytotoxic T cells (CTLs) decreases the CD4+ T cell number and consequently causes acquired immunodeficiency syndrome (AIDS) [17].…”