Human T-lymphocyte virus type I (HTLV-I)-induced myeloneuropathy in rats: oligodendrocytes undergo apoptosis in the presence of HTLV-I.
To investigate the pathogenetic role of human T-lymphocyte virus type I (HTLV-I) in central nervous system disease, a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis, designated as HAM rat disease, was examined with regard to chronological neuropathology, from early asymptomatic phase to late disease. In the thoracic spinal cord of rats with HTLV-I infection, the first event was the appearance of apoptosis of oligodendrocytes beginning at 7 months after induced infection, thereafter followed by the appearance of white matter degeneration, increase of macrophages/activated microglia and of gemistocytic astrocytes at 12, 15 and 20 months, respectively. In the spinal cord, HTLV-I provirus DNA was evident as early as 4 months after the infection, and HTLV-I pX and the tumor necrosis factor (TNF)-alpha messages began to be expressed at age 7 months, just before or at the same time as the appearance of apoptotic cells. Collective evidence suggests that the apoptotic death of oligodendrocytes, which may be induced either directly by the local expression of HTLV-I or indirectly by TNF-alpha, through the transactive function of p40Tax, is the major cause of chronic progressive myeloneuropathy in Wistar-King-Aptekman-Hokudai rats with HTLV-I infection.
Ohya
O
O
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Ikeda
H
H
Tomaru
U
U
Yamashita
I
I
Kasai
T
T
Morita
K
K
Wakisaka
A
A
Yoshiki
T
T
D000375:Aging; D000818:Animals; D017209:Apoptosis; D002353:Carrier State; D002460:Cell Line; D053938:DNA Fragmentation; D004279:DNA, Viral / Q000302:isolation & purification; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D009836:Oligodendroglia / Q000473:pathology* / Q000821:virology; D015493:Paraparesis, Tropical Spastic / Q000473:pathology* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000254:growth & development / Q000473:pathology* / Q000821:virology; D013997:Time Factors
D004279:DNA, Viral; D005904:Glial Fibrillary Acidic Protein