Summary auto-generated
This study investigates herpes simplex virus (HSV) gene expression during latency establishment and reactivation using recombinant viruses containing the lacZ reporter gene. Researchers constructed two viruses: one with lacZ controlled by the immediate early 110 (IE110) promoter and another controlled by the latency-associated promoter (LAP). Using mouse ear infection models, they tracked viral gene expression in cervical dorsal root ganglia through histochemical staining. Key findings showed that IE110 promoter activity was confined to ganglia innervating the infection site, yet latency was efficiently established in adjacent ganglia without detectable IE110 expression. During explant culture-induced reactivation, virus reactivated from all latently infected ganglia, but more efficiently from those innervating the original infection site. These results support a 'default' model of latency, where fully replication-competent virus can establish latency in the absence of lytic cycle gene expression, suggesting latency may represent a default pathway when neurons are non-permissive for lytic infection.
Key findings
- Latency-associated transcript expression was detected at all ganglionic levels from C2-C6, while IE110 promoter activity was restricted to ganglia innervating the infection site
- Efficient latency establishment occurs in ganglia without detectable IE110 gene expression during acute infection, supporting a default latency pathway model
- Virus reactivation efficiency from explanted ganglia is approximately 10-fold higher in ganglia innervating the primary infection site compared to adjacent ganglia
- Latency is established with approximately twice the frequency in primary ganglia (C2-C4) versus adjacent ganglia (C5-C6), correlating with reactivation efficiency differences
- These findings confirm that fully replication-competent HSV can establish transcriptionally active latency independent of immediate early gene expression
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Abstract
In order to facilitate an analysis of the pattern of herpes simplex virus gene expression during latency establishment and reactivation, recombinant viruses containing the lacZ reporter gene under control of either the immediate early 110 (IE110) promoter or the latency-associated promoter have been constructed. Histochemical staining of ganglia taken from mice infected with these viruses allows for the rapid identification and quantification of sensory neurones in which these two promoters are active. Using the mouse ear model, this study demonstrates that, during the establishment of latency in vivo, IE110 promoter activity is only detectable in ganglia which provide innervation to the site of virus inoculation. Latency, however, is efficiently established not only in these ganglia, but also in adjacent ganglia whose neurones do not innervate the ear, and in which there was no evidence of IE110 expression during the acute phase of infection. This implies that replication-competent virus can efficiently establish latency in the absence of detectable IE110 expression. In addition, it has been possible to investigate viral gene expression in neurones following ganglionic explant culture by monitoring IE110 promoter-driven lacZ expression within reactivating neurones. This study shows that virus can be reactivated from all latently infected ganglia, but that reactivation appears to be more efficient from ganglia which provide innervation to the site of infection. The implications of these results for the mechanisms involved in latency establishment and reactivation are discussed.