The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system

M. Kariuki Njenga, Kunihiko Asakura, Samuel F. Hunter, Peter Wettstein, Larry R Pease, Moses Rodriguez

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Infection of susceptible strains of mice with Daniel's (DA) strains of Theiler's murine encephalomyelitis virus (DAV) results in virus persistence in the central nervous system (CNS) white matter and chronic demyelination similar to that observed in multiple sclerosis. We investigated whether persistence is due to the immune system more efficiently clearing DAV from gray than from white matter of the CNS. Severe combined immunodeficient (SCID) and immunocompetent C.B-17 mice were infected with DAV to determine the kinetics, temporal distribution, and tropism of the virus in CNS. In early disease (6 h to 7 days postinfection), DAV replicated with similar kinetics in the brains and spinal cords of SCID and immunocompetent mice and in gray and white matter. DAV RNA was localized within 48 h in CNS cells of all phenotypes, including neurons, oligodendrocytes, astrocytes, and macrophages/microglia. In late disease (13 to 17 days postinfection), SCID mice became moribund and permitted higher DAY replication in both gray and white matter. In contrast, immunocompetent mice cleared virus from the gray matter but showed replication in the white matter of their brains and spinal cords. Reconstitution of SCID mice with nonimmune splenocytes or anti-DAV antibodies after establishment of infection demonstrated that both cellular and humoral immune responses decreased virus from the gray matter; however, the cellular responses were more effective. SCID mice reconstituted with splenocytes depleted of CD4+ or CD8+ T lymphocytes cleared virus from the gray matter but allowed replication in the white matter. These studies demonstrate that both neurons and glia are infected early following DAV infection but that virus persistence in the white matter is due to preferential clearance of virus from the gray matter by the immune system.

Original languageEnglish (US)
Pages (from-to)8592-8601
Number of pages10
JournalJournal of Virology
Volume71
Issue number11
StatePublished - Nov 1997

Fingerprint

Theilovirus
central nervous system
immune system
Immune System
Central Nervous System
SCID Mice
viruses
Viruses
mice
splenocytes
spinal cord
Spinal Cord
neurons
infection
brain
Neurons
kinetics
tropisms
Tropism
astrocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Njenga, M. K., Asakura, K., Hunter, S. F., Wettstein, P., Pease, L. R., & Rodriguez, M. (1997). The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system. Journal of Virology, 71(11), 8592-8601.

The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system. / Njenga, M. Kariuki; Asakura, Kunihiko; Hunter, Samuel F.; Wettstein, Peter; Pease, Larry R; Rodriguez, Moses.

In: Journal of Virology, Vol. 71, No. 11, 11.1997, p. 8592-8601.

Research output: Contribution to journalArticle

Njenga, MK, Asakura, K, Hunter, SF, Wettstein, P, Pease, LR & Rodriguez, M 1997, 'The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system', Journal of Virology, vol. 71, no. 11, pp. 8592-8601.
Njenga, M. Kariuki ; Asakura, Kunihiko ; Hunter, Samuel F. ; Wettstein, Peter ; Pease, Larry R ; Rodriguez, Moses. / The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system. In: Journal of Virology. 1997 ; Vol. 71, No. 11. pp. 8592-8601.
@article{115e4cef47464414a3804eccba4aad94,
title = "The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system",
abstract = "Infection of susceptible strains of mice with Daniel's (DA) strains of Theiler's murine encephalomyelitis virus (DAV) results in virus persistence in the central nervous system (CNS) white matter and chronic demyelination similar to that observed in multiple sclerosis. We investigated whether persistence is due to the immune system more efficiently clearing DAV from gray than from white matter of the CNS. Severe combined immunodeficient (SCID) and immunocompetent C.B-17 mice were infected with DAV to determine the kinetics, temporal distribution, and tropism of the virus in CNS. In early disease (6 h to 7 days postinfection), DAV replicated with similar kinetics in the brains and spinal cords of SCID and immunocompetent mice and in gray and white matter. DAV RNA was localized within 48 h in CNS cells of all phenotypes, including neurons, oligodendrocytes, astrocytes, and macrophages/microglia. In late disease (13 to 17 days postinfection), SCID mice became moribund and permitted higher DAY replication in both gray and white matter. In contrast, immunocompetent mice cleared virus from the gray matter but showed replication in the white matter of their brains and spinal cords. Reconstitution of SCID mice with nonimmune splenocytes or anti-DAV antibodies after establishment of infection demonstrated that both cellular and humoral immune responses decreased virus from the gray matter; however, the cellular responses were more effective. SCID mice reconstituted with splenocytes depleted of CD4+ or CD8+ T lymphocytes cleared virus from the gray matter but allowed replication in the white matter. These studies demonstrate that both neurons and glia are infected early following DAV infection but that virus persistence in the white matter is due to preferential clearance of virus from the gray matter by the immune system.",
author = "Njenga, {M. Kariuki} and Kunihiko Asakura and Hunter, {Samuel F.} and Peter Wettstein and Pease, {Larry R} and Moses Rodriguez",
year = "1997",
month = "11",
language = "English (US)",
volume = "71",
pages = "8592--8601",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - The immune system preferentially clears Theiler's virus from the gray matter of the central nervous system

AU - Njenga, M. Kariuki

AU - Asakura, Kunihiko

AU - Hunter, Samuel F.

AU - Wettstein, Peter

AU - Pease, Larry R

AU - Rodriguez, Moses

PY - 1997/11

Y1 - 1997/11

N2 - Infection of susceptible strains of mice with Daniel's (DA) strains of Theiler's murine encephalomyelitis virus (DAV) results in virus persistence in the central nervous system (CNS) white matter and chronic demyelination similar to that observed in multiple sclerosis. We investigated whether persistence is due to the immune system more efficiently clearing DAV from gray than from white matter of the CNS. Severe combined immunodeficient (SCID) and immunocompetent C.B-17 mice were infected with DAV to determine the kinetics, temporal distribution, and tropism of the virus in CNS. In early disease (6 h to 7 days postinfection), DAV replicated with similar kinetics in the brains and spinal cords of SCID and immunocompetent mice and in gray and white matter. DAV RNA was localized within 48 h in CNS cells of all phenotypes, including neurons, oligodendrocytes, astrocytes, and macrophages/microglia. In late disease (13 to 17 days postinfection), SCID mice became moribund and permitted higher DAY replication in both gray and white matter. In contrast, immunocompetent mice cleared virus from the gray matter but showed replication in the white matter of their brains and spinal cords. Reconstitution of SCID mice with nonimmune splenocytes or anti-DAV antibodies after establishment of infection demonstrated that both cellular and humoral immune responses decreased virus from the gray matter; however, the cellular responses were more effective. SCID mice reconstituted with splenocytes depleted of CD4+ or CD8+ T lymphocytes cleared virus from the gray matter but allowed replication in the white matter. These studies demonstrate that both neurons and glia are infected early following DAV infection but that virus persistence in the white matter is due to preferential clearance of virus from the gray matter by the immune system.

AB - Infection of susceptible strains of mice with Daniel's (DA) strains of Theiler's murine encephalomyelitis virus (DAV) results in virus persistence in the central nervous system (CNS) white matter and chronic demyelination similar to that observed in multiple sclerosis. We investigated whether persistence is due to the immune system more efficiently clearing DAV from gray than from white matter of the CNS. Severe combined immunodeficient (SCID) and immunocompetent C.B-17 mice were infected with DAV to determine the kinetics, temporal distribution, and tropism of the virus in CNS. In early disease (6 h to 7 days postinfection), DAV replicated with similar kinetics in the brains and spinal cords of SCID and immunocompetent mice and in gray and white matter. DAV RNA was localized within 48 h in CNS cells of all phenotypes, including neurons, oligodendrocytes, astrocytes, and macrophages/microglia. In late disease (13 to 17 days postinfection), SCID mice became moribund and permitted higher DAY replication in both gray and white matter. In contrast, immunocompetent mice cleared virus from the gray matter but showed replication in the white matter of their brains and spinal cords. Reconstitution of SCID mice with nonimmune splenocytes or anti-DAV antibodies after establishment of infection demonstrated that both cellular and humoral immune responses decreased virus from the gray matter; however, the cellular responses were more effective. SCID mice reconstituted with splenocytes depleted of CD4+ or CD8+ T lymphocytes cleared virus from the gray matter but allowed replication in the white matter. These studies demonstrate that both neurons and glia are infected early following DAV infection but that virus persistence in the white matter is due to preferential clearance of virus from the gray matter by the immune system.

UR - http://www.scopus.com/inward/record.url?scp=0030864080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030864080&partnerID=8YFLogxK

M3 - Article

C2 - 9343217

AN - SCOPUS:0030864080

VL - 71

SP - 8592

EP - 8601

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 11

ER -