Molecular Aspects of Retroviruses Associated with Chronic Neurologic Diseases

Jacobson, S.

Abstract

The objectives of this project are to assess the involvement of human retroviruses in chronic-progressive myeloneuropathy termed HTLV-I-related myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis. These investigations have two major components: 1) the molecular/virological identification of the virus(es) that are associated with the pathogenesis of these disorders, and 2) the immunological response of the host to the identified agent(s). Parallel studies are being conducted in normal carriers of HTLV-I. Human retroviruses are isolated from cells in the peripheral blood and cerebrospinal fluid. The polymerase chain reaction is used to detect and characterize viral genes in lymphocytes and in the central nervous system. These viral genomes are being cloned and sequenced. Tissue sections from spinal cord and brain from individuals with neurological diseases also are analyzed for the presence of retroviral DNA by in situ hybridization. Immune reactivity to these agents are characterized by demonstrating virus-specific cytotoxic T cell (CTL) responses in these patients, as well as lymphoproliferative responses. CTL are generated from long-term cultures. In addition, the presence of CTL in the peripheral blood of individuals with active infection is being examined. The responding cells and the antigenic specificity of the response are being characterized.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Intramural Research (Z01)
• Project #: 1Z01NS002817-01
• Application #: 3881850
• Support Year: 1
• Fiscal Year: 1990

Institution

• Name: National Institute of Neurological Disorders and Stroke
• Country: United States

Publications

Yao, Karen; Honarmand, Somayeh; Espinosa, Alex et al. (2009) Detection of human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis. Ann Neurol 65:257-67

Yamano, Yoshihisa; Araya, Natsumi; Sato, Tomoo et al. (2009) Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. PLoS One 4:e6517

Fotheringham, Julie; Donati, Donatella; Akhyani, Nahid et al. (2007) Association of human herpesvirus-6B with mesial temporal lobe epilepsy. PLoS Med 4:e180

Fotheringham, Julie; Akhyani, Nahid; Vortmeyer, Alexander et al. (2007) Detection of active human herpesvirus-6 infection in the brain: correlation with polymerase chain reaction detection in cerebrospinal fluid. J Infect Dis 195:450-4

Hammarstedt, Maria; Ahlqvist, Jenny; Jacobson, Steven et al. (2007) Purification of infectious human herpesvirus 6A virions and association of host cell proteins. Virol J 4:101

Puccioni-Sohler, M; Yamano, Y; Rios, M et al. (2007) Differentiation of HAM/TSP from patients with multiple sclerosis infected with HTLV-I. Neurology 68:206-13

Takenouchi, Norihiro; Jones, Kathryn S; Lisinski, Ivonne et al. (2007) GLUT1 is not the primary binding receptor but is associated with cell-to-cell transmission of human T-cell leukemia virus type 1. J Virol 81:1506-10

Sibon, David; Gabet, Anne-Sophie; Zandecki, Marc et al. (2006) HTLV-1 propels untransformed CD4 lymphocytes into the cell cycle while protecting CD8 cells from death. J Clin Invest 116:974-83

Yao, Karen; Mandel, Matthew; Akyani, Nahid et al. (2006) Differential HHV-6A gene expression in T cells and primary human astrocytes based on multi-virus array analysis. Glia 53:789-98

Yao, Karen; Hisada, Michie; Maloney, Elizabeth et al. (2006) Human T lymphotropic virus types I and II western blot seroindeterminate status and its association with exposure to prototype HTLV-I. J Infect Dis 193:427-37