Human T lymphocyte virus type I-induced myeloneuropathy in rats: implication of local activation of the pX and tumor necrosis factor-alpha genes in pathogenesis.
The pathogenetic roles of human T lymphocyte virus type I (HTLV-I) and cytokines were investigated in HTLV-I-induced myeloneuropathy in Wistar-King-Aptekman-Hokudai rats. In the nervous system, pX messenger RNAs of HTLV-I were selectively expressed in the diseased spinal cord and peripheral nerves but not in the unaffected cerebrum and cerebellum, even though proviral DNAs were consistently identified in these tissues. Among several cytokines examined, mRNA expression and production of tumor necrosis factor (TNF)-alpha in the spinal cord and cerebrospinal fluid correlated positively with the development of spinal cord lesions. The collective evidence strongly suggests that selective activation of HTLV-I, in particular Tax expression and production of TNF-alpha induced by HTLV-I infection in target spinal cord and peripheral nerves, is causally related to apoptotic death of oligodendrocytes and Schwann cells, a major pathogenetic pathway of the HTLV-I-induced myeloneuropathy.
Tomaru
U
U
Department of Pathology, Hokkaido University School of Medicine Sapporo, Japan.
Ikeda
H
H
Ohya
O
O
Abe
M
M
Kasai
T
T
Yamasita
I
I
Morita
K
K
Wakisaka
A
A
Yoshiki
T
T
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002353:Carrier State; D004195:Disease Models, Animal; D016355:Genes, pX; D008969:Molecular Sequence Data; D009457:Neuroglia; D009836:Oligodendroglia; D015493:Paraparesis, Tropical Spastic / Q000209:etiology*; D010525:Peripheral Nerves / Q000821:virology; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells; D012584:Sciatic Nerve / Q000821:virology; D013116:Spinal Cord / Q000821:virology; D014018:Tissue Distribution; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000235:genetics*; D016662:Virus Integration
D014409:Tumor Necrosis Factor-alpha