The function of microtubules for the secondary envelopment of Herpes Simplex Virus in neurons

点击翻译按钮获取中文摘要

Herpes Simplex Virus type l (HSV1) establishes after initial replication in the mucosa latent infections in peripheral nervous ganglia. Rarely, HSV1 invades the central nervous system and causes Herpes encephalitis that if untreated is lethal in 70% of all cases. HSV1 capsids assemble in the cell nuclei. They acquire a primary envelope by budding at the inner nuclear membrane that is shed by fusion with the outer nuclear membrane. Cytosolic capsids are then transported to a membrane organelle where they acquire a secondary envelope by budding. The resulting infectious virions are released by secretion or cell death. We will study the secondary envelopment of HSV1 in neuronal cell culture models, and how that is related to axonal spread of an infection. Using (1) specific antibodies in fluorescence and electron microscopy, (2) digital time-lapse video microscopy with simultaneously in vivo labelling of viral structures and the cellular budding compartment during a synchronized HSV1 infection, and (3) viral mutants of the inner tegument proteins VP1/3 (UL36) and UL37 that we will generate in our HSV1-BAC, we will identify the viral and host factors that are crucial for HSV1 secondary enve-lopment in neurons. We will address the role of the microtubule network in the intraneuronal transport of subviral particles and infectious virus. The viral and host proteins that mediate microtubule transport and secondary envelopment could provide specific target structures for the development of new antiviral chemotherapy of HSV1 and other herpesviruses.