Sindbis virus-induced neuronal death is both necrotic and apoptotic and is ameliorated by N-methyl-D-aspartate receptor antagonists.
Virus infection of neurons leads to different outcomes ranging from latent and noncytolytic infection to cell death. Viruses kill neurons directly by inducing either apoptosis or necrosis or indirectly as a result of the host immune response. Sindbis virus (SV) is an alphavirus that induces apoptotic cell death both in vitro and in vivo. However, apoptotic changes are not always evident in neurons induced to die by alphavirus infection. Time lapse imaging revealed that SV-infected primary cortical neurons exhibited both apoptotic and necrotic morphological features and that uninfected neurons in the cultures also died. Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors protected neurons from SV-induced death without affecting virus replication or SV-induced apoptotic cell death. These results provide evidence that SV infection activates neurotoxic pathways that result in aberrant NMDA receptor stimulation and damage to infected and uninfected neurons.
Nargi-Aizenman
J L
JL
W. Harry Feinstone Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Griffin
D E
DE
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D009336:Necrosis; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D026902:Potassium Channel Blockers; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012845:Sindbis Virus / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium