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However, the viral infections also are related with diseases in the CNS characterized by the presence of leukocyte infiltration and inflammation, inducing a progressive damage [1], such as the progressive multifocal leukoencephalopathy with the John Cunningham virus (JC), AIDS-related dementia complex observed in HIV-1-infected patients, neurodevelopmental sequelae (mental retardation, cerebral palsy, and sensorineural hearing loss) caused by congenital cytomegalovirus (CMV) infection or cerebral mass lesions in immunocompromised adults CMV-infected, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) that affects the human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals

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In addition to these pharmacological effects, MTX interacts with genetic variants in the MTHFR gene (C677T and A1298C), which independently reduce biologically active folate levels and elevate homocysteine concentrations