Mária Benkő, Koki Aoki, Niklas Arnberg, Andrew J. Davison, Marcela Echavarría, Michael Hess, Morris S. Jones, Győző L. Kaján, Adriana E. Kajon, Suresh K. Mittal, Iva I. Podgorski, Carmen San Martín, Göran Wadell, Hidemi Watanabe and Balázs Harrach*
The citation for this ICTV Report chapter is the summary published as Benkő et al., (2022):
ICTV Virus Taxonomy Profile: Adenoviridae 2022, Journal of General Virology 103(3):001721
Corresponding author: Balázs Harrach (firstname.lastname@example.org)
Edited by: Arvind Varsani and Andrew J. Davison
Posted: November 2021
Adenoviridae is a family of viruses with non-enveloped, icosahedral virions containing linear dsDNA genomes of 25–48 kb (Table 1. Adenoviridae). Its members infect a variety of vertebrate hosts ranging from fish to humans and are allocated to six genera. Members of genus Mastadenovirus infect mammals, those of Aviadenovirus infect birds, Ichtadenovirus has a single fish adenovirus, and strains of genus Testadenovirus occur in turtles. Members of Atadenovirus occur in squamate reptiles, birds, ruminants, marsupials and tortoises, and those of Siadenovirus infect birds, frog and tortoise. The severity of infections ranges from subclinical to lethal. Adenoviruses are popular virus vectors, e.g. for vaccination against the coronavirus SARS-CoV-2.
Table 1. Adenoviridae. Characteristics of members of the family Adenoviridae
|Example||human adenovirus 5 (AC_000008), species Human mastadenovirus C, genus Mastadenovirus|
|Virion||Non-enveloped icosahedral capsids 90 nm in diameter|
|Genome||Linear, dsDNA of 25–48 kb with inverted terminal repeats|
|Translation||From capped, polyadenylated and often spliced transcripts|
|Host range||Mammals, birds, reptiles, amphibians and fish; host range varies among genera|
|Taxonomy||Realm Varidnaviria, kingdom Bamfordvirae, phylum Preplasmiviricota, class Tectiliviricetes, order Rowavirales; 6 genera containing 87 species|
Adenovirus (AdV) virions are non-enveloped particles, 90 nm in diameter. The characteristic icosahedral capsid has a pseudo T=25 triangulation number and consists of 240 non-vertex capsomers (hexons), 8–10 nm in diameter, and 12 vertex capsomers (penton bases), from which fibers protrude (Figure 1. Adenoviridae) (van Raaij et al., 1999). The 240 hexons are formed by the interaction of three identical proteins (designated II) and consist of two distinct parts: a triangular top with three “towers”, and a pseudohexagonal base with a central cavity. The hexon bases are tightly packed, forming a protein shell that protects the inner components. The 12 penton bases are each formed by the interaction of five copies of protein III and are tightly associated with the fibers, which are homotrimers of protein IV. The fibers have three structural domains, including the tail, which binds to the penton base, the shaft of characteristic length and the distal knob (San Martín 2012). The length of fibers examined ranges from 9 to 77.5 nm. Human adenovirus 40 and human adenovirus 41 have fibers of two different lengths that occur alternately on the vertices. Human adenovirus 52 and many simian adenoviruses (SAdVs) also have fibers of two different lengths (Jones et al., 2007, Lenman et al., 2015), and some SAdVs even have three different fibers (Abbink et al., 2015). Members of the genera Aviadenovirus and Atadenovirus may have more than one fiber inserted at a single vertex (Gelderblom and Maichle-Lauppe 1982, Pénzes et al., 2014). In members of the genus Mastadenovirus, protein IX is located on the outer part of the capsid, cementing the hexon proteins in each facet (12 copies of IX per facet). In human adenoviruses (HAdVs), protein IX also links two facets together across the icosahedral edge (Liu et al., 2010). Protein IX is not present in the members of the other genera. An atadenovirus-specific protein, LH3, has a similar structural role to IX, though a distantly related structure (Gorman et al., 2005, Pantelic et al., 2008). Proteins IIIa, VI and VIII are located internally. Five IIIa monomers are arranged in a ring underneath each vertex (penton base). Protein VI is located beneath the hexons and is not arranged in icosahedral symmetry. There are six monomers of protein VIII per facet: three are wedged between protein IIIa and the peripentonal hexons, and the other three are arranged around the icosahedral 3-fold symmetry axis, contributing with protein IX to the stabilization of the facet (Liu et al., 2010). The core consists of the DNA genome complexed with four proteins: V, VII, X (also known as mu or µ) and terminal protein (TP). Protein V is found only in mastadenoviruses. A few copies of the maturation protease (L3 23K, adenovirus protease/AVP/adenain) are packaged bound to the genome (Mangel and San Martín 2014).
|Figure 1. Adenoviridae (A) The icosahedral adenovirus capsid. Left: model prepared by low resolution cryo-electron microscopy with penton bases highlighted in yellow and fibers in dark blue (from (van Raaij et al., 1999)). The shaded triangle indicates one facet. Right: schematic figure indicating the position of the major and minor coat proteins in the facet, as solved by cryo-electron microscopy of the mastadenovirus human adenovirus 5 (Liu et al., 2010). (B) Non-icosahedral components. A segment has been removed from the map in (A) to reveal the core. For detailed description of the capsid and core proteins see text. As the structure of the nucleoprotein core has not been established, the polypeptides associated with the DNA are shown in hypothetical locations. Panels A and B reproduced from (San Martín 2012).|
Physicochemical and physical properties
Virion Mr is 150–180×106; buoyant density in CsCl is 1.31–1.36 g cm−3. Viruses are stable on storage in the frozen state. They are insensitive to lipid solvents. Human adenovirus 5 (HAdV-5) partially disassembles at pH 6. Heat sensitivity varies among the genera (Bartha and Kisary 1970).
The genome is a single, linear molecule of dsDNA that contains inverted terminal repeats (ITRs) at both ends. TP is covalently linked to the 5′-end of each DNA strand. The size of the genomes sequenced to date ranges between 24,630 and 48,395 bp, with ITRs of 26–721 bp. The G+C content of the genome varies widely between 33.24 and 66.92%. The genetic organization of the central part of the genome is well conserved throughout the family, whereas the regions near the ends exhibit large variations in length and gene content (Figure 2. Adenoviridae) (Davison et al., 2003b, Doszpoly et al., 2019).
|Figure 2. Adenoviridae Schematic illustration of the various genome organizations found in members of different adenovirus genera. Black arrows depict coding sequences conserved in every genus, grey arrows show those present in more than one genus, and coloured arrows show coding sequences of genus-specific proteins. Proteins without identified function are named according to ORF number, but the ORF prefix is omitted for clarity. White rectangles show direct repeat regions and inverted terminal repeats (ITRs; not clearly visibly when very short). Thin lines connect the exons of spliced genes. Aviadenovirus (fowl adenovirus 1) ORF2, ORF12, ORF13 and ORF14 are homologues of parvovirus (family Parvoviridae) NS1, whereas MDV lipase is homologous to Marek's disease virus (family Herpesviridae) lipase.|
About 40 different viral polypeptides are produced (Table 2. Adenoviridae). Almost one-third of these compose the virion, including a virus-encoded cysteine protease (23 kDa) that is necessary for the processing of some precursor proteins (prefixed with p) (Pérez-Berná et al., 2014). With the exception of proteins V and IX, the structural proteins are well conserved in every genus (Davison et al., 2003b, Doszpoly et al., 2019).
Table 2. Adenoviridae. Proteins encoded by human adenovirus 2
|13, 27, 32||E1A||R||Only in mastadenoviruses|
|16, 21||E1B||R||Only in mastadenoviruses|
|55||E1B||R||Only in mastadenoviruses|
|59||E2A||D; 72 kDa* DBP|
|120||E2B||D; 140 kDa* DNA pol|
|75||E2B||S; 87 kDa* pTP†|
|4, 7, 8, 10, 12||E3||H||Only in mastadenoviruses|
|13, 15, 15, 19|
|7, 13, 13, 14||E4||R||Only in mastadenoviruses|
|15||E4||R; 31 kDa* dUTPase||Only in some mast- and aviadenoviruses|
|17||E4||R; 34 kDa*||Only in mast- and atadenoviruses; present on the capsid at a single location|
|47||L1||D;† 52/55 kDa*|
|64||L1||D, S (pIIIa);† p-protein|
|63||L2||S (III); penton base*|
|22||L2||S (pVII);† major core|
|42||L2||S (V); minor core||Only in mastadenoviruses|
|10||L2||S (pX);† X/µ|
|109||L3||S (II); hexon|
|23||L3||D, S; protease|
|90||L4||D; 100 kDa*|
|25||L4||D, R; 33 kDa* p-protein|
|22||L4||D, R; 22 kDa* p-protein, shares first 105 amino acid residues with L4 33K|
|62||L5||S (IV); fiber|
|14||Intermediate||S (IX)||Only in mastadenoviruses|
|51||Intermediate||D, S (IVa2)|
Molecular masses are rounded to the nearest 1000, and are presented as unmodified and uncleaved gene products. D = DNA synthesis and packaging; DBP = DNA-binding protein; DNA pol = DNA polymerase; H = subverting host defence mechanisms; p = precursor; p-protein = phosphoprotein; R = regulation, S = structural; TP = terminal protein; * = Mr values are significantly different from those obtained by SDS-PAGE; † = cleaved by viral protease. L4 33K is present in the empty capsid, and DBP is present both in empty and mature virions (Ahi et al., 2015).
Fiber proteins and some of the nonstructural proteins are glycosylated.
Genome organization and replication
Virus entry into cells occurs by attachment via the fiber knob to various receptors (Arnberg 2012, Lenman et al., 2015, Lenman et al., 2018, Stasiak and Stehle 2020) and subsequent internalization via interaction between the penton base and cellular αv integrins (Smith et al., 2010, Greber and Flatt 2019, Pied and Wodrich 2019). Protein VI mediates the release of virions from endosomes, allowing dynein-mediated transport on microtubules to nuclear pores. After uncoating, the virus core is delivered to the nucleus, which is the site of virus transcription, DNA replication and virion assembly (Hoeben and Uil 2013, Condezo and San Martín 2017). Virus infection mediates the early shut-off of host DNA synthesis and, later, synthesis of host mRNA as well as polypeptide synthesis. Transcription by host RNA polymerase II involves both DNA strands of the virus genome, and initiates (in human adenovirus 2 [HAdV-2]) from promoters of the five early regions (E1A, E1B, E2, E3 and E4), two genes of intermediate proteins (IX and IVa2), the major late promoter (L) as well as the U exon protein (UXP) late promoter (Figure 3. Adenoviridae. All primary transcripts are capped and polyadenylated. Complex splicing generates families of mRNAs, and the proteins are produced via these complex splicing mechanisms (Figure 3. Adenoviridae). In primate mastadenoviruses, there are one or two virus-associated (VA) RNA genes, which are transcribed by RNA polymerase III. These encode RNA products that facilitate translation of late mRNAs and block the cellular interferon response. Similar VA RNA genes have not been identified in other adenoviruses. In some fowl adenoviruses, the existence of one VA RNA gene, at a different genome position, has been described, but these VA RNAs are not homologous to mastadenovirus VA RNAs (Chiocca et al., 1996). Products of the four early (E) regions of mastadenovirus genomes (E1 to E4) facilitate extensive modulation of the host cell transcriptional machinery (E1, which is often considered as two regions [E1A and E1B] and E4), comprise the virus DNA replication complex (E2), and provide means for subverting host defence mechanisms (E3). E2 is well conserved throughout the family, whereas the length and gene content of E1, E3 and E4 exhibit great variability even within genera (Figure 2. Adenoviridae). Intermediate proteins (IX and IVa2) and late (L) gene products (L1–L5) are concerned with virion assembly and maturation (Ahi and Mittal 2016, Ahi et al., 2017).
|Figure 3. Adenoviridae Schematic illustration of the transcription pattern of human adenovirus 2. The parallel lines indicate the linear dsDNA genome of 36 kb. The dots, broken lines and split arrows indicate the spliced structures of the mRNAs. E1A, E1B, E2A, E2B, E3 and E4 refer to early transcription units (red arrows). Most (but not all) late genes (blue arrows) are in the major late transcription unit, which initiates after the E1B and protein IX genes on the rightward transcribed strand, and which includes the L1, L2, L3, L4 and L5 families of mRNAs. Intermediate genes (encoding protein IX and protein IVa2) are shown by light blue arrows. (Adapted from (Wold and Gooding 1991)).|
The natural host range of adenoviruses has been thought to be confined to a single host species (e.g. members of the species Human mastadenovirus D are restricted to humans), or to evolutionarily closely related species (e.g. bovine adenovirus 2, which is confined to cattle and sheep). This also applies to cells in culture. However, there is now evidence that numerous adenoviruses can cross host species barriers. A typical example is skunk adenovirus 1, which was first described in Canada and has also been detected in diseased or dead African pigmy hedgehogs in Japan and the USA, North American porcupines and grey fox, and even in a New World monkey in Hungary (Kozak et al., 2015, Madarame et al., 2019, Needle et al., 2019a, Balik et al., 2020, Doszpoly et al., 2020, Needle et al., 2020). According to its phylogenetic relationships and the arrangement of genes in the E3 region, this virus may have originated from a bat. Similarly, canine adenovirus 1 (CAdV-1) has been detected not only in dogs but also in multiple carnivore species, wolves, various fox species, raccoons, bears and skunks (Balboni et al., 2019). A broader host range is often observed in members of genera Atadenovirus and Siadenovirus, where a host switch may have played an important role in the evolutionary history. For example, the atadenovirus snake adenovirus 1 occurs in corn snake, boa and python (Benkő et al., 2002, Farkas et al., 2008), and snake adenovirus 2 has been detected in eastern corn snake, California kingsnake and asp viper (Garner et al., 2008). Furthermore, both of these snake adenovirus types occur in tortoises (Salzmann et al., 2021). The siadenovirus psittacine adenovirus 2 has been described in representatives of a dozen species of the order Psittaciformes (Wellehan et al., 2009, Ballmann and Vidovszky 2013, Phalen et al., 2019, Yang et al., 2019), whereas the siadenovirus raptor adenovirus 1 has been found in Harris’s hawk and two owl species (Zsivanovits et al., 2006, Kovács and Benkő 2011).
Some human adenoviruses (HAdVs, mainly members of the species Human mastadenovirus C) productively infect rodent or ruminant cells. HAdVs of species Human mastadenovirus A and Human mastadenovirus B manifest high and low oncogenicity, respectively, in newborn hamsters, whereas the other HAdVs are not oncogenic. The majority of HAdV infections in humans are subclinical but can result in virus shedding for years due to persistent infection of lymphocytes. Direct or indirect transmission occurs from throat, faeces, eye, urine or fomites, depending on the virus type. Certain HAdV types (listed below in parentheses) are predominantly associated with specific pathology, such as acute respiratory infections (HAdV-1 to -5, -7, -14, -21) (Robinson et al., 2011, Hage et al., 2014, Kajon et al., 2019), adenoidal–pharyngeal conjunctivitis (HAdV-3, -4, -7, -14), epidemic keratoconjunctivitis (HAdV-8, -19, -37, -53, -54, -56) (Walsh et al., 2009, Aoki et al., 2019), hepatitis (HAdV-5) or venereal disease (HAdV-37). HAdV-40 and HAdV-41 can be detected in high yield from faeces of young children with acute gastroenteritis and are second only to rotaviruses as a major cause of infantile viral diarrhoea. HAdV-11, -34 and -35 cause persistent interstitial infection in the kidney and haemorrhagic cystitis, occurring most frequently in immuno-suppressed patients after stem cell or solid organ transplantation. The most severe and frequently lethal infections in primary immunodeficiencies and paediatric allogeneic hematopoietic stem cell transplantation are caused by members of species Human mastadenovirus A, Human mastadenovirus B and Human mastadenovirus C, HAdV-31 (Human mastadenovirus C) being most common. Patients with secondary immunodeficiency can also be at risk when infected by members of these three species, which can cause different manifestations of disseminated disease. Fatal liver disease can develop after infection with HAdV-1, -2 or -5 (Lion 2014). Serotypes from HAdV-42 to HAdV-51 of species Human mastadenovirus D have been all isolated from AIDS patients but do not cause severe disease.
Mastadenovirus infections are common in other mammals, but disease usually appears only if predisposing factors (e.g. management problems, crowding, shipping or concurrent bacterial infections) are present. CAdV-1 seems to be an exception, in that it is the causative agent of infectious canine hepatitis (Rubarth's disease), a life-threatening disease of puppies, and of encephalitis in foxes. A closely related virus, canine adenovirus 2 (CAdV-2), causes infectious laryngotracheitis (kennel cough) in dogs, and this disease is common in breeder stocks. Adenoviruses infecting susceptible cells cause similar cytopathic effects, i.e. early rounding of cells and aggregation or lysis of chromatin, followed by the later appearance of characteristic eosinophilic or basophilic nuclear inclusions.
Hepatitis-hydropericardium syndrome predominantly in chickens has been associated with fowl adenovirus 4 (FAdV-4). This disease occurs mainly in Asia and causes great economic losses. Gizzard erosion in chickens is caused by fowl adenovirus 1, whereas inclusion body hepatitis is caused by fowl adenovirus 2, fowl adenovirus 8a, fowl adenovirus 8b or fowl adenovirus 11 in various species of birds (Schachner et al., 2018). Duck adenovirus 1 is the causative agent of egg drop syndrome of chickens. The disease causes dramatic decrease in the egg production of laying flocks. Turkey adenovirus 3 (genus Siadenovirus) causes turkey haemorrhagic enteritis (Pitcovski et al., 1998, Palya et al., 2007).
HAdV-5 has been engineered and used extensively as a gene delivery vector (Alonso-Padilla et al., 2016). Other serotypes (including non-human ones) are being developed to overcome the problem posed by pre-existing neutralizing antibodies in the population, and also to achieve better targeting of specific organs and tissues (Both 2004, Dicks et al., 2012, Abbink et al., 2015, Junyent and Kremer 2015, Alonso-Padilla et al., 2016, Corredor et al., 2017, Del Rio et al., 2019, Sayedahmed et al., 2019, Lu et al., 2020). Recently, chimpanzee adenovirus-based vector vaccines have been developed against very important human pathogens, such as Ebola virus (Filoviridae) and SARS-CoV-2 (Coronaviridae) (Ledgerwood et al., 2017, Folegatti et al., 2020).
In the past, adenovirus serotypes were differentiated on the basis of neutralization assays (Mennechet et al., 2019). A serotype is defined as an adenovirus that either exhibits no cross-reaction with other adenoviruses or shows a homologous:heterologous titer ratio greater than 16 (in both directions). For homologous:heterologous titer ratios of 8 or 16, a serotype assignment is made if either the viral hemagglutinins are unrelated (as shown by lack of cross-reaction in hemagglutination-inhibition tests) or if substantial biophysical, biochemical or phylogenetic differences exist. Antigens at the surface of the virion are mainly type-specific. Hexons are involved in neutralization, and fibers in neutralization and hemagglutination-inhibition. Soluble antigens associated with virus infections include surplus capsid proteins that have not been assembled. As defined using monoclonal antibodies, hexons and other soluble antigens carry numerous epitopes that can be genus-, species- or type-specific. Free hexon protein reacts mainly as a genus-specific antigen. The genus-specific antigen is located on the basal surface of the hexon, whereas serotype-specific antigens are located mainly on the tower region (Adám et al., 1998).
Genus demarcation criteria
Genus designation depends on the following characteristics:
- Phylogenetic distance (based primarily on maximum likelihood analysis of the DNA polymerase amino acid sequence)
- Genome organization (presence or lack of certain characteristic genes or transcription units)
- Host range
Derivation of names
Adenoviridae: from the Greek aden, adenos, meaning “gland”; in recognition of the fact that adenoviruses were first isolated from human adenoid tissue.
Atadenovirus: from adenine and thymine, in recognition that the genomes of the first recognized members of the genus (from ruminant, avian and marsupial hosts) have a remarkably high A+T content.
Aviadenovirus: from the Latin avis, meaning “bird”.
Ichtadenovirus: from the Greek ichthys, meaning “fish”.
Mastadenovirus: from the Greek mastos, meaning “breast” referring to mammal host.
Platyrrhini mastadenovirus A: from the Latin platyrrhini, meaning “flat-nosed” , applied to the New World monkey hosts of members of this species.
Siadenovirus: from sialidase, in recognition that members of the genus have a putative sialidase homologue.
Testadenovirus: from the Latin testudo, meaning “tortoise”.
Relationships within the family
High-resolution genomic data have provided insights into the molecular evolution of adenoviruses. Consistent with specific characteristics of genome organization, molecular phylogenetic analysis results in clear separation of six different clusters corresponding to the six accepted genera (Mastadenovirus, Aviadenovirus, Atadenovirus, Siadenovirus, Ichtadenovirus and Testadenovirus; Figure 4. Adenoviridae) (Doszpoly et al., 2013, Doszpoly et al., 2019, Harrach et al., 2019). Within the genera, phylogenetic relationships among the viruses are usually similar to those among their hosts, i.e. the tree topologies of the viruses and the hosts are often congruent (Chen et al., 2011, Ballmann and Harrach 2016, Podgorski et al., 2018, Harrach et al., 2019, Kaján et al., 2020). An interesting example is a common clade of adenoviruses from animals belonging to the order Artiodactyla clade Cetruminantia (cetaceans and ruminants) (Standorf et al., 2018, Harrach et al., 2019). Phylogenetic analyses have revealed separable phylogroups among isolates or strains of the same serotype, such as human adenovirus 4 (HAdV-4) (Gonzalez et al., 2019).
|Figure 4. Adenoviridae Phylogenetic tree of representative members of adenovirus species based on maximum likelihood analysis of the complete amino acid sequences of DNA-dependent DNA polymerase. Multiple alignment: MultAlin; model selection: ProtTest 2.4; maximum likelihood calculation: PhyML 3.1 with model LG+I+G and branch support Shimodaira-Hasegawa (SH) on the Galaxy/Pasteur platform. Unrooted calculation; white sturgeon adenovirus 1 and red-eared slider adenovirus 1 were selected as an outgroup for visualization. The bar indicates 20% difference between two neighbouring sequences. SH branch support values shown at the nodes. Viruses are represented by GenBank accession number, virus name with type or strain designation, and species name. Genus names are indicated. This phylogenetic tree and corresponding sequence alignment are available to download from the Resources page.|
Against this coevolutionary background, there are some exceptional cases of very distantly related adenoviruses infecting the same host. In particular, the adenovirus types isolated from cattle, sheep, deer or birds appear on very distant branches, and even in separate clusters corresponding to different genera (Ballmann and Harrach 2016, Duarte et al., 2019, Harrach et al., 2019, Sutherland et al., 2019, Vidovszky et al., 2019). Thus, it appears that multiple host switches may also have occurred (Harrach et al., 2019). For example, it is probable that adenoviruses from scaled reptiles switched to ruminants and birds (Benkő and Harrach 2003, Wellehan et al., 2004), adenoviruses from bats switched to carnivores (causing fatal disease in dogs) (Kohl et al., 2012) and horses (Vidovszky et al., 2015), and adenoviruses from Old World monkeys and apes switched to humans (Hoppe et al., 2015). Duck adenovirus 1 (DAdV-1) switched from ducks to chickens.
Relationships with other taxa
A dsDNA bacteriophage Enterobacteria phage PRD1 (family Tectiviridae), shares a similar virion architecture (a pseudo T=25 icosahedral capsid with fiber-like projections at the vertices) with adenoviruses (Butcher et al., 1995). The 15 kb genome of PRD1 has ITRs and contains genes encoding terminal protein and DNA polymerase arranged in the same order as in adenoviruses. Moreover, the terminal protein also acts as primer in PRD1 DNA replication. A study of the structure of the main capsid proteins (P3 of PRD1 and the hexon of adenoviruses) revealed a very similar fold (a double jelly roll orthogonal to the capsid surface) and further strengthened an evolutionary link between the two viruses (Benson et al., 1999). Such a double-jelly-roll fold has been found in many virus capsids (San Martín and van Raaij 2018).
In fungi and plants, a linear plasmid (called yeast killer plasmid) occurs either in the cytoplasm or in the mitochondria that has adenovirus-like features (an ITR and a TP gene adjacent to a DNA polymerase gene). Based on the established or predicted three-dimensional structures of their major capsid proteins and on sharing of a characteristic ATPase, sulfolobus turreted icosahedral virus (family Turriviridae), which infects a crenarchaeal host (in domain Archaea), and also two archaeal proviruses (TKV4 and MVV) could also be placed into the PRD1-adenovirus lineage (Krupovic and Bamford 2008). These archaeal proviruses (TKV4 and MVV) are integrated into the 5′- and 3′-distal regions of tRNA genes of the euryarchaeal species Thermococcus kodakaraensis (strain KOD1) and Methanococcus voltae (A3), respectively.
Adenoviruses also show some similarity to other viruses. The fibers of many adenovirus types use the same cellular receptor (coxsackievirus and adenovirus receptor, CAR) for attachment as coxsackie B viruses (family Picornaviridae) (Arnberg 2012). Adenovirus fibers have been reported to show structural similarity to reovirus attachment protein sigma 1, which binds the junction adhesion molecule (JAM) receptor (Chappell et al., 2002). Adenoviruses may occur together with adenovirus-dependent parvoviruses, for which they may provide helper functions (Pénzes et al., 2020a). Similarity was observed between certain proteins coded by the E3 region of HAdVs and the RL11 gene family of human cytomegalovirus (family Herpesviridae) (Davison et al., 2003a). The primary structure of the p32K protein, which is characteristic of atadenoviruses, has similarity to bacterial small acid-soluble proteins (SASPs) commonly found in various spore-forming bacteria (Élő et al., 2003). The atadenovirus LH3 capsid protein has a beta-helix fold typical of receptor binding spikes in tailed bacteriophages (Menéndez-Conejero et al., 2017). Recent studies have proposed the existence of novel virus families for adomaviruses and adintoviruses, which are related to adenoviruses on the basis of several homologous genes (Starrett et al., 2021).
Examination of the deepest phylogeny of the family suggests an origin from bacterial viruses by descent from non-replicating polintons in the mitochondria that became replicating adenoviruses in vertebrates only (Koonin et al., 2015, Krupovic and Koonin 2015). These distant similarities, which are focused primarily on the structural conservation of part of the hexon in other viruses, led to the establishment of the following higher taxa incorporating the family Adenoviridae: realm Varidnaviria, kingdom Bamfordvirae, phylum Preplasmaviricota, class Tectiliviricetes (to which also the family Tectiviridae belongs), order Rowavirales (Koonin et al., 2020, Walker et al., 2020).
Related, unclassified viruses
|Virus name||Accession number||Virus abbreviation|
|crocodile adenovirus 1|
Adenovirus-caused hepatitis has been described in crocodile hatchlings of about 2 weeks old that were bred on a commercial farm in South Africa (Pfitzer et al., 2019). The hatchlings showed typical clinical signs of hepatitis, and the identification of intranuclear inclusion bodies in the liver was used to differentiate between adenovirus-caused hepatitis and chlamydial hepatitis. However, no sequence data are available.