Abstract
Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral sites, such as epithelial tissues, and then enter neurons of the peripheral nervous system (PNS), where lifelong latency is established. Following reactivation from latency and assembly of new viral particles, the infection typically spreads back out towards the periphery. These spread events result in the characteristic lesions (cold sores) commonly associated with herpes simplex virus (HSV) and herpes zoster (shingles) associated with varicella zoster virus (VZV). Occasionally, the infection spreads transsynaptically from the PNS into higher order neurons of the central nervous system (CNS). Spread of infection into the CNS, while rarer in natural hosts, often results in severe consequences, including death. In this review, we discuss the viral and cellular mechanisms that govern directional spread of infection in the nervous system. We focus on the molecular events that mediate long distance directional transport of viral particles in neurons during entry and egress.
Highlights
AlphaherpesvirinaeHerpesviruses are characterized by a large double-stranded DNA genome, a complex enveloped virion and the ability to establish a latent phase as part of their lifecycle in their hosts [1]
Herpesviruses are characterized by a large double-stranded DNA genome, a complex enveloped virion and the ability to establish a latent phase as part of their lifecycle in their hosts [1].The mammalian herpesviruses belong to the Herpesviridae family and can be classified into three subfamilies, including the alphaherpesvirinae, betaherpesvirinae and gammaherpesvirinae
Final maturation occurs by envelopment of viral particles into vesicles derived from the trans-Golgi network (TGN) that contain viral and host membrane proteins
Summary
Herpesviruses are characterized by a large double-stranded DNA genome, a complex enveloped virion and the ability to establish a latent phase as part of their lifecycle in their hosts [1]. Members of each subfamily are distinguished based on their genome content, the cell type where latency is established in the host and the length of their productive replication cycle [1]. Alphaherpesviruses have the broadest host range [1]. These viruses are pantropic and neuroinvasive [2,3]. Once in the peripheral or central nervous system, infection can spread within chains of synaptically connected neurons. This review addresses the molecular mechanisms underlying neuronal invasion and directional spread of alphaherpesvirus infections
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