DAD conceived and designed the study, performed the animal studies and participated in drafting and editing the manuscript. All authors read and approved the final 3-MA mouse manuscript.”
“Background Several evidences indicate that a viral infection could be involved in the aetiology of demyelinating learn more diseases, such as Multiple Sclerosis (MS) [1]. Several members of the Herpesviridae family, including Herpes simplex virus type 1 (HSV-1), have been suggested as possible causes of this pathology [2, 3]. Oligodendrocytes, the myelin-producing glial cells in the central nervous system, have proven to be susceptible to this alphaherpesvirus in vivo[4–7] and in cultured cells [8]. Therefore, to

deepen the knowledge on HSV-1 infection of myelinating cells, will contribute in this website clarifying relevant aspects of demyelination aetiology. HSV-1 is a highly prevalent neurotropic human pathogen that can infect and establish latency in neurons. HSV-1 can cause, in certain circumstances, severe pathologies such as keratoconjunctivitis and encephalitis. Following primary infection of epithelial cells, virions spread to neurons and establish latent infections in the trigeminal ganglia. The morphogenesis of HSV-1 has been broadly studied

[9–11], but several events of this complex process remain unsolved. Viral transcription, replication, packaging of the new viral particles and formation of nucleocapsids all take place in the nucleus of the infected cell. Thereafter, DNA-containing capsids acquire a primary envelope when they enter the perinuclear space by budding into the inner nuclear membrane, followed by a subsequent Baf-A1 purchase de-envelopment process through the outer nuclear membrane [12]. Once in the cytoplasm, the nucleocapsids acquire their inner tegument [13]. Finally, virion assembly concludes through a secondary envelopment process by budding into trans-Golgi network (TGN)-derived

vesicles coated with viral glycoproteins and more tegument proteins [14]. During this process, virions acquire the outer tegument and the envelope. Although this model of envelopment/de-envelopment/re-envelopment is widely accepted [15, 16], many aspects of the process remain to be unravelled, specifically those concerning the molecular tools that HSV-1 uses to exploit the cellular trafficking machinery. Small GTPase Rab27 [17–19] subfamily consists –in vertebrates– of two isoforms, Rab27a and Rab27b, which display a high homology. Both isoforms, although differing in cell type specificity, have been implicated in regulated exocytosis and might play a key role in certain events of membrane trafficking. Rab27a and Rab27b are functionally redundant but display differential expression in tissues: while Rab27a is mainly expressed in a broad range of secretory cells [20], melanocytes, endocrine cells and cytotoxic T lymphocytes (CTLs), Rab27b is expressed in platelets, endocrine cells, spleen and brain, being absent in melanocytes and CTLs [21].