ICTV Virus Taxonomy Profile: Herpesviridae 2021

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125–241 kbp contain 70–170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.


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Abstract
Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv. global/ report/ herpesviridae.

VIRION
Virions consist of a core, capsid, tegument and envelope (Table 1, Fig. 1) [1]. The core comprises the viral genome packaged into the capsid as a linear, dsDNA molecule. The capsid is a T=16 icosahedron containing 162 capsomers arranged as 150 hexons, 11 pentons and one portal. The tegument consists of inner and outer layers. The lipid envelope contains integral viral glycoproteins forming a network of spikes.

GENOME
The genome is 125-241 kbp. The arrangement of direct or inverted repeats at the termini or internally results in several classes of genome architecture. The genome contains 70-170 genes encoding proteins, 43 of which are shared across the family, suggesting a common replication strategy [2]. Additional genes encoding nontranslated RNAs may be present.

REPLICATION
Herpesviruses have been discovered in a wide range of vertebrates (reptiles, birds and mammals). The most extensively studied animals are host to members of several species. Most herpesviruses have coevolved and sometimes cospeciated within a single host lineage, although foundational cross-species transmission events appear to have occurred. In general, lytic infection involves attachment and penetration by the interaction of virion envelope proteins with cell surface receptors, followed by entry via membrane fusion at the cell surface or after endocytosis (Fig. 2) [3,4]. The capsid uncoats and is transported to a nuclear pore, and the genome enters the nucleus. Transcription occurs in a kinetic cascade: immediate early genes encode regulatory functions, early genes encode the DNA replication complex and a variety of proteins involved in modifying host cell metabolism or immune responses, and late genes primarily encode virion proteins. Viral DNA synthesis occurs by a rolling-circle replication mechanism to generate concatemers, from which genomes are cleaved and packaged into capsids. Capsids bud through the inner nuclear membrane and are then de-enveloped by fusion with the outer nuclear membrane and released into the cytoplasm. Assembly of tegument proteins and secondary envelopment to generate mature virions occur in a Golgi or post-Golgi compartment. Virions exit the cell by exocytosis or cell-to-cell spread.
Herpesviruses are restricted in their natural host range and highly adapted to their hosts, with severe infection usually observed only in the foetus, the very young, the immunocompromised or in an alternative host. Typically, a primary, systemic infection is established via a cell-associated viraemia, followed by a latent phase in which dormant virus occasionally reactivates. Herpesviruses operate a range of modulation mechanisms to manage host immunity.

TAXONOMY
Current taxonomy: ictv. global/ taxonomy. The family Herpesviridae includes three subfamilies, and belongs to the order Herpesvirales along with the families Alloherpesviridae and Malacoherpesviridae. This order is in turn classified alongside the order Caudovirales in the kingdom Heunggongvirae.

RESOURCES
Current ICTV Report on the family Herpesviridae: ictv. global/ report/ herpesviridae.

Funding information
Production of this Profile, the ICTV Report and associated resources was funded by a grant from the Wellcome Trust (WT108418AIA).