The egress of alphaherpesviruses from the cell

A commonly accepted concept in herpesvirology holds that herpesvirions are formed by budding of nucelocapsids at the inner nuclear membrane and the enveloped virions are released into the perinuclear space (see Chapter II. A. 9). This is a closed compartment that virions need to exit, in order to reach the extracellular space and start a new infection cycle. How alphaherpesviruses accomplish this gaol is a controversial issue. Of the two pathways of virus exit proposed, the single envelopment and the double envelopment, also referred to as deenvelopment-reenvelopment, each has evidence and supporters in the literature (the topic has been covered in excellent reviews and papers (Enquist et al., 1998; Skepper et al., 2001; Johnson & Huber, 2002; Mettenleiter, 2002). Part of the uncertainties that still dominate this topic comes from the difficulties in interpreting static electron microscopy images. Thus, cytoplasmic virions juxtaposed to curved vesicles were interpreted in some studies as evidence for secondary envelopment, i.e for deenvelopment-reenvelopment, and in other studies as evidence of fusion of the virion envelope with encasing vesicles, i.e. as deenvelopment (Campadelli-Fiume et al., 1991; Roizman & Knipe, 2001). To solve these ambiguities, several approaches have been undertaken in recent years, including the generation of genetically modified mutants and cytochemistry.