Abstract: Dendritic cells (DCs) function as a link between innate and adaptive immune responses. 9
Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to propagate 10
infection. Coinfection of HTLV-1 and HIV-1 has implications for cancer malignancies. Both viruses 11
initially infect DCs and propagate the infection to CD4+ T cells through cell-to-cell transmission 12
using mechanisms including the formation of virologic synapses, viral biofilms, and conduits. These 13
retroviruses are both neurotrophic with neurovirulence determinants. The neuropathogenesis of 14
HIV-1 and HTLV-1 results in neurodegenerative diseases such as HIV-associated neurocognitive 15
disorders (HAND) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). 16
Infected DCs are known to traffic to the brain (CNS) and periphery (PNS, lymphatics) to induce 17
neurodegeneration in HAND and HAM/TSP patients. Elevated levels of neuroinflammation have 18
been correlated with cognitive decline and impairment of motor control performance. Current vac- 19
cinations and therapeutics for HIV-1 and HTLV-1 are assessed and can be applied to patients with 20
HIV-1 associated cancers and adult T cell leukemia/lymphoma (ATL). These diseases caused by co- 21
infections can result in both neurodegeneration and cancer. There are associations with cancer ma- 22
lignancies and HIV-1 and HTLV-1 as well as other human oncogenic viruses (EBV, HBV, HCV, 23
HDV, and HPV). This review contains current knowledge on DC sensing of HIV-1 and HTLV-1 24
including DC-SIGN, Tat, Tax, and current viral therapies. An overview of DC interaction with on- 25
cogenic viruses including EBV, Hepatitis viruses, and HPV is also provided. Vaccines and thera- 26
peutics targeting host-pathogen interactions can provide a solution to co-infections, neurodegener- 27
ation, and cancer.
Decoding pathogenesis factors
Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a...