Critical role for protein tyrosine phosphatase SHP-1 in controlling infection of central nervous system glia and demyelination by Theiler's murine encephalomyelitis virus.
We previously characterized the expression and function of the protein tyrosine phosphatase SHP-1 in the glia of the central nervous system (CNS). In the present study, we describe the role of SHP-1 in virus infection of glia and virus-induced demyelination in the CNS. For in vivo studies, SHP-1-deficient mice and their normal littermates received an intracerebral inoculation of an attenuated strain of Theiler's murine encephalomyelitis virus (TMEV). At various times after infection, virus replication, TMEV antigen expression, and demyelination were monitored. It was found that the CNS of SHP-1-deficient mice uniquely displayed demyelination and contained substantially higher levels of virus than did that of normal littermate mice. Many infected astrocytes and oligodendrocytes were detected in both brains and spinal cords of SHP-1-deficient but not normal littermate mice, showing that the virus replicated and spread at a much higher rate in the glia of SHP-1-deficient animals. To ascertain whether the lack of SHP-1 in the glia was primarily responsible for these differences, glial samples from these mice were cultured in vitro and infected with TMEV. As in vivo, infected astrocytes and oligodendrocytes of SHP-1-deficient mice were much more numerous and produced more virus than did those of normal littermate mice. These findings indicate that SHP-1 is a critical factor in controlling virus replication in the CNS glia and virus-induced demyelination.
Department of Neurology, Upstate Medical University, State University of New York, Syracuse 13210, USA. massap@upstate.edu
Paul T
PT
Massa
Stacie L
SL
Ropka
Sucharita
S
Saha
Karen L
KL
Fecenko
Kathryn L
KL
Beuler
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000821:virology; D001921:Brain / Q000473:pathology / Q000821:virology; D018188:Cardiovirus Infections / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000821:virology; D002494:Central Nervous System Infections / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000821:virology; D003711:Demyelinating Diseases / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000821:virology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009457:Neuroglia / Q000201:enzymology / Q000821:virology; D009836:Oligodendroglia / Q000201:enzymology / Q000821:virology; D010243:Paralysis / Q000201:enzymology / Q000209:etiology / Q000821:virology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D017945:Theilovirus / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse