Age-dependent pathogenesis of murine gammaherpesvirus 68 infection of the central nervous system.
Gammaherpesvirus infection of the central nervous system (CNS) has been linked to various neurological diseases, including meningitis, encephalitis, and multiple sclerosis. However, little is known about the interactions between the virus and the CNS in vitro or in vivo. Murine gammaherpesvirus 68 (MHV-68 or (gamma)HV-68) is genetically related and biologically similar to human gammaherpesviruses, thereby providing a tractable animal model system in which to study both viral pathogenesis and replication. In the present study, we show the successful infection of cultured neuronal cells, microglia, and astrocytes with MHV-68 to various extents. Upon intracerebroventricular injection of a recombinant virus (MHV-68/LacZ) into 4-5-week-old and 9-10-week-old mice, the 4-5-week-old mice displayed high mortality within 5-7 days, while the majority of the 9-10-week-old mice survived until the end of the experimental period. Until a peak at 3-4 days post-infection, viral DNA replication and gene expression were similar in the brains of both mouse groups, but only the 9-10-week-old mice were able to subdue viral DNA replication and gene expression after 5 days post-infection. Pro-inflammatory cytokine mRNAs of tumor necrosis factor-alpha, interleukin 1beta, and interleukin 6 were highly induced in the brains of the 4-5-week-old mice, suggesting their possible contributions as neurotoxic factors in the agedependent control of MHV-68 replication of the CNS.
Cho
Hye-Jeong
HJ
Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea.
Kim
Sungbum
S
Kwak
Sung-Eun
SE
Kang
Tae-Cheon
TC
Kim
Hee-Sung
HS
Kwon
Hyung-Joo
HJ
Kim
Yoon-Won
YW
Kim
Yong-Sun
YS
Choi
Eun-Kyung
EK
Song
Moon Jung
MJ
D000375:Aging / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000821:virology; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility; D018142:Gammaherpesvirinae / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000821:virology*; D018836:Inflammation Mediators / Q000378:metabolism; D007276:Injections, Intraventricular; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000821:virology; D009474:Neurons / Q000821:virology; D051381:Rats; D016019:Survival Analysis; D014779:Virus Replication / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators