Components of Adenovirus Genome Packaging

Abstract

Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging.

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

“…However, many viral structural proteins and packaging are excluded from VRCs, localizing instead throughout the nucleoplasm, at the periphery of the nucleus, or at distinct foci [103,145,165]. The adenovirus 52-55K protein is transiently incorporated into assembling viral particles, and it is required for either the packaging or retention of viral genomes [165][166][167][168]. A recent study has identified the viral late protein 52-55K, as well as assembled virions and assembly intermediates at the periphery of the VRC where Ad genome replication takes place, suggesting that adenovirus particles are assembled and packaged at these sites [165].…”

“…This suggests that the transcription of viral genomes and viral RNA processing occurs in proximity to the PRZ. Adenovirus is believed to package its genomes into pre-formed capsids, as described by a sequential model of packaging similar to HSV-1 or certain bacteriophages [76,166,168]. However, recent findings identify viral DNA, the 52-55K packaging protein, formed particles, and proposed assembly intermediates within the PRZ [165].…”

Viral and cellular interactions during adenovirus DNA replication

“…In addition, one end of the genome also contains a packaging sequence (ψ) proximal to the ITR. This ψ can be bound by viral packaging proteins and is required for encapsulation (packaging) of the viral genome within the viral particle . Viral genomes present within capsids also have two copies of a mature form of the viral terminal protein (TP) covalently attached to the 5′ ends, resulting from the addition of pTP during replication and its subsequent proteolytic cleavage during virion maturation .…”

“…However, it is uncertain to what extent these phenotypes may also be influenced by the proposed role of nucleophosmin during viral genome replication . It is also noteworthy that although prevailing dogma suggests HAdV packages its genomes into preformed capsids as described by a sequential model of packaging , there is also evidence to support an alternate packaging model. A recent study that included immunofluorescence and EM identified viral DNA, the 52–55 K packaging protein, and formed particles, as well as putative assembly intermediates, within the PRZ, leading to the suggestion that the PRZ is not only the site of viral DNA replication, but also the site of assembly and packaging .…”

In vitro methods for testing antiviral drugs

“…Nuclear export is specific and depends on the presence of nuclear export signals (NES) in the transported proteins. One example of a nonenveloped icosahedral virus that assembles in the nucleus is adenovirus, the assembly of which has been studied intensely due to its potential use in gene therapies [reviewed in (Ahi and Mittal, 2016)]. Recent data suggest that upon accumulation of multiple copies of adenoviral dsDNA genomes, coordinated assembly and packaging occur by two interlinked mechanisms that involve both capsid proteins and core components (Condezo and San Martín, 2017).…”