HTLV-1 Induced Molecular Mimicry in Neurological Disease

Pearls & Oy-sters: “Not multiple sclerosis” and the changing face of HTLV-1

“…The most widely reported neurologic manifestation of this condition is slowly progressive myelopathy, which may clinically resemble primary progressive multiple sclerosis (MS). 1,7,8 Extraspinal manifestations have been mostly limited to case reports and include cerebellar tremor, cognitive impairment, leukoencephalopathy, and optic neuritis.…”

“…[2][3][4][5] Classically, patients infected with HTLV-1 develop HAM/TSP, a slowly progressive myelopathy characterized by spastic paraparesis, hyperreflexia, and early bladder symptoms. 5,[6][7][8][9] Recent data suggest that clinicians should broaden their definition of HTLV-1-associated neurologic disease. 2,5,9 Specifically, several articles show that a significant proportion of patients develop extraspinal neurologic manifestations, including cerebellar syndromes, optic neuritis, intellectual impairment, and uveitis.…”

Antibody Transfection into Neurons as a Tool to Study Disease Pathogenesis

“…The ability to produce highly specific antibodies to target proteins has allowed for very precise biological questions to be addressed. Importantly, antibodies have been implicated in the pathogenesis of a number of human diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), paraneoplastic syndromes, multiple sclerosis (MS) and human T-lymphotropic virus type 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/ TSP) [1][2][3][4][5][6][7][8][9] . How antibodies cause disease is an area of ongoing investigation, and data suggests that interactions between antibodies and various intracellular molecules results in inflammation, altered cellular messaging, and apoptosis 10 .…”

“…It has been shown that patients with MS and HAM/ TSP produce autoantibodies to the intracellular RNA binding protein heterogeneous ribonuclear protein A1 (hnRNP A1) 3, 5-7, 9, 11 . Recent data indicate that antibodies to both intra-neuronal and surface antigens are pathogenic 3,[5][6][7][8][9]11 . Thus, a procedure that allows for the study of intracellular antibody:protein interactions would lend great insight into disease pathogenesis.…”

The Role of HTLV-1 in Alteration of Immune Regulation Through Regulatory T Cell Dysfunction and Exosomal Manipulation

“…Indeed, HAM/TSP patients have been demonstrated to have a higher infiltrate of HTLV-1 Tax specific CTLs in both the peripheral blood, CSF, and CNS lesions as compared to ACs (Elovaara et al, 1993;Kubota et al, 2002;Matsuura et al, 2015). Interestingly, Tax has been reported to share structural homology with a host cellular protein called heterogeneous nuclear ribonuclear protein-A1(hnRNP-A1) (Lee et al, 2005). Antibodies from HAM/TSP patient CSF cross-reacted with this protein, which was also found to be expressed on the surface of neurons .…”