Family: Adenoviridae

Genus: Mastadenovirus

Distinguishing features

Mastadenoviruses infect mammals only, and have been distinguished traditionally from members of other adenovirus genera by serology (since genus members share complement-fixing antigen). Only mastadenoviruses have proteins IX and V. 

Virion

Morphology

See discussion under family properties. The 3D structures of the virions of human adenovirus 5 (HAdV-5, species Human mastadenovirus C) and human adenovirus 26 (HAdV-26, species Human mastadenovirus D) have been determined (Liu et al., 2010, Yu et al., 2017), as well as those of the fibers of different viruses from the genus including animal mastadenoviruses like porcine adenovirus 4 and murine adenovirus 2 (van Raaij et al., 1999, Guardado-Calvo et al., 2010, Singh et al., 2018). 

Physicochemical and physical properties

Virus infectivity is inactivated after heating at 56°C for more than 10 min. 

Nucleic acid

Mastadenovirus genomes fully sequenced to date range between 27,952 (polar bear adenovirus 1) and 37,860 bp (simian adenovirus 31.2 from chimpanzee, species Human mastadenovirus C) (Roy et al., 2009, Böszörményi et al., 2020). Nucleotide composition varies between 34.20 (bat adenovirus 10 strain WIV18) (Tan et al., 2017) and 63.84% G+C (porcine adenovirus 3). The inverted terminal repeats (ITRs) of mastadenoviruses are in general longer, at 35–368 bp (bat adenovirus 4 strain WIV9 and bovine adenovirus 10) (Dán et al., 2001, Tan et al., 2016), and more complex (containing a variety of cellular factor-binding sites) than in members of other genera. The genome of human adenovirus 2 (HAdV-2) is 35,937 bp with a nucleotide composition of 55.20% G+C, and the ITR is 103 bp. Nucleic acid detection (mainly by PCR) has essentially replaced serology as the preferred diagnostic method (Echavarria et al., 2001). 

Proteins

The unique structural proteins of mastadenoviruses are proteins V and IX. Protein IX is responsible for cementing the hexons on the outer surface of the capsid. Interestingly, polar bear adenovirus 1 lacks protein IX (Dayaram et al., 2018, Böszörményi et al., 2020). 

Lipids

None reported. 

Carbohydrates

HAdV-2 and HAdV-5 fibers contain O-linked N-acetylglucosamine, which has not been found in the fiber of human adenovirus 7 (HAdV-7) (Mullis et al., 1990). 

Genome organization and replication

Genome organization, replication and splicing have been most extensively studied for isolates of the species Human mastadenovirus C (Figure 3. Adenoviridae) (Davison et al., 2003b, Zhao et al., 2014), and the findings seem to be generally applicable to all mastadenoviruses, except in the E3 and E4 regions (Hemmi et al., 2011, Cortés-Hinojosa et al., 2015, Podgorski et al., 2016, Abendroth et al., 2017, Ridpath et al., 2017). 

The E3 region is most complex in the primate mastadenoviruses and contains up to eight genes (e.g. the chimpanzee adenovirus types of species Human mastadenovirus E, such as simian adenovirus 25 [SAdV-25]). This early region is also different in the non-primate mastadenoviruses, e.g. in the bat mastadenoviruses (Ogawa et al., 2017, Jansen van Vuren et al., 2018, Kobayashi et al., 2019). The E3 region is also considerably shorter and less complex in the non-primate mastadenoviruses. The simplest E3 region, comprising a single gene, occurs in murine adenovirus 1 (MAdV-1) and murine adenovirus 3 (MAdV-3). In the E4 region, a single homologue of the HAdV-2 34K protein exists in almost all mastadenoviruses but is duplicated in bovine adenovirus 3 and porcine adenovirus 5 (Ahi et al., 2017). 

The genes coding protein IX and V occur only in mastadenoviruses. Protein IX, as well as cementing the hexons on the outer surface of the capsid, also acts as a transcriptional activator, takes part in nuclear re-organization, and is involved in the final stages of virus entry (Strunze et al., 2011). However, the protein IX gene is missing from polar bear adenovirus 1, as identified in deceased polar bears in two independent cases in Berlin and Budapest (Dayaram et al., 2018, Böszörményi et al., 2020). Protein V is not only a core protein but, in association with cellular protein p32, is involved in transport of viral DNA into the nucleus of the infected cell. 

Although the fiber knobs of most mastadenoviruses bind to coxsackievirus and AdV receptor (CAR), CD46, desmoglein-2 or sialic acid (Marttila et al., 2005, Wang et al., 2011), porcine adenovirus 4 fiber has an additional C-terminal galectin domain connected to the head by an RGD-containing sequence, and binds carbohydrates containing lactose and N-acetyl-lactosamine units (Guardado-Calvo et al., 2010, Liu et al., 2020). 

Human adenovirus 52 (HAdV-52, species Human mastadenovirus G) is one of only three known human mastadenoviruses (the other two are human adenovirus 40 [HAdV-40] and human adenovirus 41 [HAdV-41], both species Human mastadenovirus F) that are equipped with both a long and a short fiber (Jones et al., 2007), whereas there is an entire lineage of monkey mastadenoviruses that have this feature (Podgorski et al., 2016). The long fiber of HAdV-52 binds to CAR, and the short fiber knob can use polysialic acid as a receptor on target cells, indicating a dual tropism (Lenman et al., 2018). Similarly, the long fiber of HAdV-40 and HAdV-41 is also CAR-binding, but the short fiber uses heparin sulphate as the cellular receptor (Rajan et al., 2021). 

Biology

See discussion under family properties. Recently, a novel adenovirus was described associated with necrotizing bronchiolitis in a captive reindeer (Dastjerdi et al., 2021). 

Antigenicity

Genus members share complement-fixing antigen. Besides the hexon, the penton base has been identified as a second immunodominant target in human mastadenoviruses (Tischer et al., 2016). See further discussion under family properties. 

Species demarcation criteria

Species demarcation is based on evolutionary distance as reflected by the calculated phylogenetic distances and genome organizational differences. Several species contain multiple similar types (designated by Arabic numbers) that were traditionally distinguished serologically (by virus neutralization). The serological type demarcation criterion is currently being replaced by genomic criteria. Species designation depends on at least two of the following characteristics:

• Phylogenetic distance (>10–15%, based on distance matrix analysis of the DNA polymerase amino acid sequence)
• Genome organization (characteristically in the E3 region)
• Nucleotide composition
• Host range
• Oncogenicity in rodents
• Cross-neutralization
• Ability to recombine
• Number of VA RNA genes
• Hemagglutination

For example, if virus neutralization data are available, lack of cross-neutralization combined with a phylogenetic distance of >15% separates two types into different species. If the phylogenetic distance is between 10 and 15%, any additional common grouping criteria from the list above may classify separate types into the same species even if they were isolated from different hosts. As an example, the most numerous types from the same host, the human mastadenoviruses, can be clearly separated into seven species supported by phylogenetic analysis, their ability to recombine (e.g. between human adenovirus 1, HAdV-2, HAdV-5 and human adenovirus 6), growth characteristics (e.g. HAdV-40 and HAdV-41 show similar restricted capacity), oncogenicity and nucleotide composition (e.g. human adenovirus 12, human adenovirus 18 and human adenovirus 31, which are members of the species Human mastadenovirus A, share high oncogenicity in rodents and low % G+C content). Mastadenoviruses of species Human mastadenovirus D have only been isolated from humans, whereas Human mastadenovirus A also includes isolates from chimpanzee, Human mastadenovirus B includes isolates from chimpanzee and gorilla, Human mastadenovirus C includes isolates from bonobo, chimpanzee and gorilla. Human mastadenovirus E includes isolates from bonobo and chimpanzee, and Human mastadenovirus F includes isolates from chimpanzee, gorilla and moustached monkey (Lange et al., 2019). Human mastadenovirus G includes many Old World monkey isolates (but not a single ape isolate) and a single human serotype, human adenovirus 52 (for further details on hosts see: https://sites.google.com/site/adenoseq/). Ape mastadenoviruses are classified into species otherwise including only human isolates because they are adequately similar to certain human mastadenoviruses according to species demarcation criteria (Roy et al., 2009). These lineages originated in apes and switched host to humans, in which they were first discovered (Hoppe et al., 2015). 

Thus far, >100 human adenovirus genotypes have been proposed from whole genome sequencing data, including homologous recombinants with unique combinations of earlier identified versions of penton base, hexon and fiber genes. Clearly, the situation is nuanced, and the precise rules and type demarcation criteria for genotypes are still under discussion. 

Member species

The Member Species table enumerating important virus exemplars classified under each species of the genus is provided at the bottom of the page.

Related, unclassified viruses

Virus names and virus abbreviations are not official ICTV designations. 

Many mastadenoviruses have been detected in samples from exotic or wild animals by a DNA polymerase-based consensus PCR (Wellehan et al., 2009), by a IVa2-based consensus PCR (Pantó et al., 2015), or by PCR based on other genes, and no further molecular data are known (Li et al., 2010, Hall et al., 2012, Kim et al., 2017, Lakatos et al., 2017, Argüello-Sánchez et al., 2018, Iglesias-Caballero et al., 2018, Diakoudi et al., 2019, Diffo et al., 2019, Côrte-Real et al., 2020, De Luca et al., 2021). Nonetheless, this minimal information is sufficient to reveal these sequences represent mastadenoviruses, and longer sequences are needed for robust species classification (Hofmann-Sieber et al., 2020). Metagenomic studies of animal tissues or faecal samples usually result only in partial sequences (Geldenhuys et al., 2018, Wu et al., 2018). Nonetheless, there are viruses (e.g., Gould’s wattled bat adenovirus, reindeer adenovirus 1) for which whole genome sequences have been determined from metagenomic sequencing, and these are respectable candidates for classification into novel species (Rogers et al., 2020, Dastjerdi et al., 2021).