Nuclear Localization of the C1 Factor (Host Cell Factor) in Sensory Neurons Correlates with Reactivation of Herpes Simplex Virus from Latency

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 4; pp. 1229 - 1233
• Main Authors: Kristie, Thomas M., Vogel, Jodi L., Sears, Amy E.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 16.02.1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Animals; Biochemistry; Biological Sciences; Cell Nucleus - metabolism; Coatomer Protein; Ganglia; Gene expression regulation; Gene Expression Regulation, Viral; Genes; Genes, Immediate-Early; Herpes simplex virus; Herpes Simplex Virus Protein Vmw65 - metabolism; Herpes viruses; Host Cell Factor C1; Membrane Proteins - chemistry; Membrane Proteins - isolation & purification; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Nerve Growth Factors - pharmacology; Neurons; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Neurons, Afferent - virology; Organ Culture Techniques; Organ Specificity; Perceptual localization; Protein Biosynthesis; Proteins; Proteins - analysis; Proteins - physiology; Receptors, Cytoplasmic and Nuclear; Scarification; Sensory neurons; Simplexvirus; Simplexvirus - physiology; Transcription Factors; Trigeminal ganglion; Trigeminal Ganglion - physiology; Trigeminal Ganglion - virology; Virus Activation - physiology; Virus Latency
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.4.1229

After a primary infection, herpes simplex virus is maintained in a latent state in neurons of sensory ganglia until complex stimuli reactivate viral lytic replication. Although the mechanisms governing reactivation from the latent state remain unknown, the regulated expression of the viral immediate early genes represents a critical point in this process. These genes are controlled by transcription enhancer complexes whose assembly requires and is coordinated by the cellular C1 factor (host cell factor). In contrast to other tissues, the C1 factor is not detected in the nuclei of sensory neurons. Experimental conditions that induce the reactivation of herpes simplex virus in mouse model systems result in rapid nuclear localization of the protein, indicating that the C1 factor is sequestered in these cells until reactivation signals induce a redistribution of the protein. The regulated localization suggests that C1 is a critical switch determinant of the viral lytic-latent cycle.