Remodeling of host membranes during herpesvirus assembly and egress

Abstract

Many viruses, enveloped or non-enveloped, remodel host membrane structures for their replication, assembly and escape from host cells. Herpesviruses are important human pathogens and cause many diseases. As large enveloped DNA viruses, herpesviruses undergo several complex steps to complete their life cycles and produce infectious progenies. Firstly, herpesvirus assembly initiates in the nucleus, producing nucleocapsids that are too large to cross through the nuclear pores. Nascent nucleocapsids instead bud at the inner nuclear membrane to form primary enveloped virions in the perinuclear space followed by fusion of the primary envelopes with the outer nuclear membrane, to translocate the nucleocapsids into the cytoplasm. Secondly, nucleocapsids obtain a series of tegument proteins in the cytoplasm and bud into vesicles derived from host organelles to acquire viral envelopes. The vesicles are then transported to and fuse with the plasma membrane to release the mature virions to the extracellular space. Therefore, at least two budding and fusion events take place at cellular membrane structures during herpesviruses assembly and egress, which induce membrane deformations. In this review, we describe and discuss how herpesviruses exploit and remodel host membrane structures to assemble and escape from the host cell.

Keywords: assembly; budding; egress; fusion; herpesviruses; membrane deformations.

Figure 1

A schematic representation of herpesvirus assembly and egress. In the nucleus, newly synthesized viral genomes are packaged into the capsids (1). The nascent nucleocapsids traffic to the inner nuclear membrane (INM) where nuclear egress complex (NEC) are anchored and the nuclear lamina has been dissolved by host or viral kinases (2). Nucleocapsids bud at the INM, forming primary enveloped virions in the perinuclear space (3, primary envelopment). The primary envelopes of virions then fuse with the outer nuclear membrane (ONM), releasing the nucleocapsids into the cytoplasm (4, deenvelopment). In the cytoplasm, nucleocapsids acquire tegument proteins at electron-dense deposits, which is obvious in transmission electron microscopy micrograph (5). The tegumented capsids bud into special vesicles (6) that may derive from trans-Golgi network (TGN), early endosome (EE) or autophagosome, and form mature virions inside vesicles (7, secondary envelopment). Finally, these vesicles fuse with the plasma membrane and release mature virions to extracellular space (8)