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Virology (MD PhD) (Subject) / Fräfel (Lesson)
- Replication-conditional HSV-1-based vector - used against brain tumors, as the neurons are postmitotic and the virus targets only the mitotic tumor
- Replication-defective HSV-1 gene therapy - non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1 - ability to express genes after having established latent infections - proficient candidates for therapeutic gene transfer settings in neurons
- HSV-1 latency - circular DNA assembled in nucleosomal chromatin - All viral genes except for LAT (latency associated transcript) are silenced (involvement of CoREST/REST repressor complex). - LAT expression: encodes several RNA species, miRNA, no protein. LAT overlaps ICP0 and ICP4 genes. Hypothesis: miRNA or siRNA silencing of lytic genes. Reactivation- Latent virus can periodically reactivate and establish a lytic infection, usually at the site of the primary infection. Reactivation stimuli: stress, UV-light, fever, etc.
- Alphaherpesviridae - HSV-1, HSV-2, VZV - variable host range - short replication cycle, rapid spread in culture - latency primarily but not exclusively in neurons
- Betaherpesvirinae - CMV, HHV-6, HHV-7 - restricted host range - slow replication cycle and slow spread in culture - latency in secretory glands, lymphoreticular cells, kidney, ... - infected cells become large (cytomegalia)
- Gammaherpesvirinae - EBV, HHV-8 (KSHV) - restricted host range - in vitro, all members replicate in lymphoblastoid cells - replicate in either B- or T-cells - latency frequently in lymphoid tissues
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