9th International Adenovirus Meeting - April 26-30, 2009, Dobogókő, Hungary

 

ADENOVIRUS TAXONOMY

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Official taxonomy of adenoviruses since August 2009. (Summay: short list)
Benkö M, Harrach B, Both GW, Russell WC, Adair BM, Adám E, de Jong JC, Hess M, Johnson M, Kajon A, Kidd AH, Lehmkuhl HD,
Li Q.-G, Mautner V, Pring-Akerblom P, Wadell G (2005) Family Adenoviridae. Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball
LA (eds): Virus Taxonomy. VIIIth Report of the International Committee on Taxonomy of Viruses. Elsevier, New York pp 213-228

and update based on 2008 and the August 2009 decisions of ICTV (in bold)

 

Graphical representation of the available adenovirus sequences shows also the isolates not even at tentative species status. (The tentative species level will be diminished in the next ICTV Report as a non-official taxon.)

 

Family           Adenoviridae

Taxonomic Structure of the Family

Family                   Adenoviridae

Genus                                Mastadenovirus

Genus                                Aviadenovirus

Genus                                Atadenovirus

Genus                                Siadenovirus

Genus                                Ichtadenovirus

 

Genome Structure

 

Figure 1:  Schematic illustration of the different genome organizations found in members of the four well characterized genera.  Black arrows depict genes conserved in every genus, gray arrows show genes present in more than one genus, colored arrows show genus-specific genes.

 

Genus           Mastadenovirus

Type Species               Human adenovirus C

Distinguishing Features

Mastadenoviruses infect mammals only, and can be distinguished from members of other adenovirus genera serologically.  Virus infectivity is inactivated after heating at 56°C for more than 10 min.  The size of mastadenovirus genomes fully sequenced to date ranges between 30,288 and 36,521 bp.  The G+C content of the DNA varies between 40.8 and 63.8%.  The ITRs of mastadenoviruses are considerable longer (93 to 371 bp) and more complex (containing a variety of cellular factor binding sites) than in members of the other genera.  HAdV-2 comprises 35,937 bp and its ITR is 103 bp long.

 

Unique proteins of mastadenoviruses are protein V and IX, and most of those coded by the E1A, E1B, E3, and E4 regions.  Protein IX, besides cementing the hexons on the outer surface of the capsid, was demonstrated to act as a transcriptional activator, and it also takes part in the nuclear re-organization.  Protein V is a core protein which, in association with cellular protein p32, seems to be involved in the transport of viral DNA into the nucleus of the infected cell.  The E3 and E4 proteins are often different also in the different species of mastadenoviruses.

 

The genome organization and replication is best studied for isolates of species Human adenovirus C, but those findings seem to be generally applicable to all mastadenoviruses except the organization of the E3 and E4 regions.  These early regions are different in the animal adenoviruses.  In the E4 region, only a homolog of the 34K protein of HAdV-2 seems to exist in all mastadenoviruses and is even duplicated in Bovine adenovirus 3 and Porcine adenovirus 5.  The E3 region is also considerably shorter and simpler in the animal adenoviruses.  The simplest E3 is in Murine adenovirus 1 containing a single 12.5K homolog.

List of Species Demarcation Criteria in the Genus

The serologically distinguishable serotypes (synonym of types, designated by Arabic numbers) are being grouped into species.  Species name reflects the first described host complemented by a letter if there are more than one adenovirus species bearing the same host name.  The data available at present suggest the separation of at least 19 species within the genus.  Several virus types listed as “Tentative Species in the Genus” need further study before being placed into the existing or additional species.

 

Species designation depends on several of the following characteristics:

·         Calculated phylogenetic distance (more than 5-10% based primarily on the distance matrix analysis of the protease, pVIII, hexon, and DNA polymerase aa sequence comparisons)

·         DNA hybridization

·         RFLP analysis

·         Percentage of GC in the genome

·         Oncogenicity in rodents

·         Growth characteristics

·         Host range

·         Cross-neutralization

·         Possibility of recombination

·         Number of VA RNA genes

·         Haemagglutination

·         Genetic organization of the E3 region

 

The lack of cross neutralization combined with a calculated phylogenetic distance of more than 10% separates two serotypes into different species.  If the phylogenetic distance is less than 5%, any additional common grouping criteria from the above may classify separate serotypes into the same species even if they had been isolated from different hosts.  For example, numerous properties of Bovine adenovirus 2 (BAdV-2), including results of the distance matrix analyses on protease and hexon aa sequences, RFLP analysis, GC content of the genome, DNA hybridization, ability to infect sheep, all implied its close relationship with Ovine adenovirus 2, 3, 4, and 5, and were therefore placed in a common species.  Similarly, BAdV-9 proved to be almost indistinguishable from HAdV-2 and 5 based on partial sequencing, DNA hybridization, and restriction enzyme fragment profile.  BAdV-1, 3, and 10, however, show considerable evolutionary distance from BAdV-2, 9, and from each other (more than 10%). In addition, they share only limited sequence homology detectable by DNA hybridization, possess very differently organized E3 region and consequently they should be seen as separate species.  The most numerous serotypes from the same host, the human adenoviruses, can be clearly separated into 6 species along the old subgenus lines supported by distance matrix analysis.  HAdV-1, 2, 5, 6 may recombine with each other; HAdV-40 and 41 show similar restricted growth characteristics; the members of former subgenus A (HAdV-12, HAdV-18 and HAdV-31) share high oncogenicity in rodents and low G+C percentage in their genome.  Adenoviruses isolated from chimpanzee resemble certain HAdVs in such extent that they are classified into “Human” adenovirus species.  Simian adenovirus 22 to 25 (SAdV-22–25) belong to the species Human adenovirus E, while SAdV-21 belongs to Human adenovirus B.

List of Species in the Genus

Species in the Genus

Bovine adenovirus A

abbreviation

Bovine adenovirus 1

(BAdV-1)

Bovine adenovirus B

 

Bovine adenovirus 3

(BAdV-3)

Bovine adenovirus C

 

Bovine adenovirus 10

(BAdV-10)

Canine adenovirus

 

Canine adenovirus 1

(CAdV-1)

Canine adenovirus 2

(CAdV-2)

Equine adenovirus A

 

Equine adenovirus 1

(EAdV-1)

Equine adenovirus B

 

Equine adenovirus 2

(EAdV-2)

Human adenovirus A

 

Human adenovirus 12

(HAdV-12)

Human adenovirus 18

(HAdV-18)

Human adenovirus 31

(HAdV-31)

Human adenovirus B

 

Human adenovirus 3

(HAdV-3)

Human adenovirus 7

(HAdV-7)

Human adenovirus 11

(HAdV-11)

Human adenovirus 14

(HAdV-14)

Human adenovirus 16

(HAdV-16)

Human adenovirus 21

(HAdV-21)

Human adenovirus 34

(HAdV-34)

Human adenovirus 35

(HAdV-35)

Human adenovirus 50

(HAdV-50)

Simian adenovirus 21

(SAdV-21)

Human adenovirus C

 

Bovine adenovirus 9

(BAdV-9)

Human adenovirus 1

(HAdV-1)

Human adenovirus 2

(HAdV-2)

Human adenovirus 5

(HAdV-5)

Human adenovirus 6

(HAdV-6)

Human adenovirus D

 

Human adenovirus 8

(HAdV-8)

Human adenovirus 9

(HAdV-9)

Human adenovirus 10

(HAdV-10)

Human adenovirus 13

(HAdV-13)

Human adenovirus 15

(HAdV-15)

Human adenovirus 17

(HAdV-17)

Human adenovirus 19

(HAdV-19)

Human adenovirus 20

(HAdV-20)

Human adenovirus 22–30

(HAdV-22–30)

Human adenovirus 32

(HAdV-32)

Human adenovirus 33

(HAdV-33)

Human adenovirus 36–39

(HAdV-36–39)

Human adenovirus 42–49

(HAdV-42–49)

Human adenovirus 51

(HAdV-51)
          Human adenovirus 53                (HAdV-53)
          Human adenovirus 54                (HAdV-51)

Human adenovirus E

 

Human adenovirus 4

(HAdV-4)

Simian adenovirus 22

(SAdV-22)

Simian adenovirus 23

(SAdV-23)

Simian adenovirus 24

(SAdV-24)

Simian adenovirus 25

(SAdV-25)

Human adenovirus F

 

Human adenovirus 40

(HAdV-40)

Human adenovirus 41

(HAdV-41)

Simian adenovirus 19

(SAdV-19)
Human adenovirus G  
          Human adenovirus 52

(HAdV-52)
          Simian adenovirus 1

(SAdV-1)
          Simian adenovirus 7

(SAdV-7)

Murine adenovirus A

 

Murine adenovirus 1

(MAdV-1)
Murine adenovirus C  
          Murine adenovirus 3

(MAdV-3)

Ovine adenovirus A

 

Bovine adenovirus 2

(BAdV-2)

Ovine adenovirus 2

(OAdV-2)

Ovine adenovirus 3

(OAdV-3)

Ovine adenovirus 4

(OAdV-4)

Ovine adenovirus 5

(OAdV-5)

Ovine adenovirus B

 

Ovine adenovirus 1

(OAdV-1)

Porcine adenovirus A

 

Porcine adenovirus 1

(PAdV-1)

Porcine adenovirus 2

(PAdV-2)

Porcine adenovirus 3

(PAdV-3)

Porcine adenovirus B

 

Porcine adenovirus 4

(PAdV-4)

Porcine adenovirus C

 

Porcine adenovirus 5

(PAdV-5)
Simian adenovirus A  
          Simian adenovirus 3

(SAdV-3)

Tree shrew adenovirus

 

Tree shrew adenovirus 1

(TSAdV-1)

Tentative Species in the Genus

Goat adenovirus

 

Goat adenovirus 2

(GAdV-2)

Guinea pig adenovirus

 

Guinea pig adenovirus 1

(GPAdV-1)

Murine adenovirus B

 

Murine adenovirus 2

(MAdV-2)

Ovine adenovirus C

 

Ovine adenovirus 6

(OAdV-6)

Simian adenovirus*

 

Simian adenovirus 1–18

(SAdV-1–18)

Simian adenovirus 20

(SAdV-20)

Squirrel adenovirus

 

Squirrel adenovirus

(SqAdV-1)

*  From simian adenoviruses, the chimpanzee types (SAdV-21–25) and monkey AdVs SAdV-1, 3, and 7 could unambiguously be classified into species.  Based on partial DNA sequence data, the remaining old world monkey adenovirus types cluster into several putative species.  SAdV-19 (probably along with some other types) belongs to HAdV-F.  SAdVs yet unassigned to species are provisionally shown as members of a single tentative species until further evidences for their proper classification are provided.

 

Genus           Aviadenovirus

Type Species               Fowl adenovirus A

Distinguishing Features

Aviadenoviruses are serologically distinct from members of the other adenovirus genera and they only infect birds.  The virions contain two fibers per vertex.  Fowl adenovirus type 1 (FAdV-1) has two fiber genes, and two projections of considerably different lengths in each penton base.  Other FAdVs also have two fibers, but apparently only one fiber gene, and the fiber shafts are of similar lengths.  The long fiber of FAdV-1 uses coxsackievirus and adenovirus receptor (CAR) for attachment to the cell.

 

The DNA of aviadenoviruses is considerably (20 to 45%) larger in size compared to that of mastadenoviruses.  Two aviadenovirus (FAdV-1 and FAdV-9) genomes, which were fully sequenced, comprise 43,804 and 45,063 bp, respectively, representing the longest adenoviral DNA molecules known to date.  The G+C content of partial or full sequences of aviadenovirus genomes varies between 53.8 and 59%.  The sequenced ITRs are 54 and 71 bp long.

 

The genomic organization of aviadenoviruses is also different (Fig. 2).  The genes of protein V and IX are missing, as well as homologues of mastadenoviral early regions E1 and E3.  The E4 region seems to be translocated resulting in the dUTP pyrophosphatase (dUTPase, not present in every mastadenovirus) being the first gene on the left end of the genome in aviadenoviruses studied to date.  The organization of the central part of the genome containing the late genes and the E2 region is similar to that of mastadenoviruses.  The right end of the genome contains several transcription units, which are unique for aviadenoviruses.  The majority of genes and proteins from this region have not yet been characterized in detail.  A novel protein GAM-1 of FAdV-1 was demonstrated to have an antiapoptotic effect, and to activate heat-shock response in the infected cell.  GAM-1, in synergism with another novel protein, encoded by ORF22, binds the retinoblastoma protein and can activate the E2F pathway.  Additional, yet uncharacterized predicted gene products were found to show homology with proteins of other viruses, like the nonstructural protein NS1 (syn. Rep protein) of parvoviruses, or a triacylglycerol lipase, a homolog of which also occurs in an avian herpesvirus (Marek’s disease virus).

 

Aviadenoviruses possess no common complement-fixing antigen with the members of the other genera.  There exist isolates where serum neutralization cannot differentiate clearly the serotypes.  The introduction of 8a and 8b was deemed necessary because of the inconsistency in the type numbering scheme used in different countries and continents over the years.  Newer results have not yet confirmed unambiguously the distinctness of different isolates typed as FAdV-8a and b.  Avian adenoviruses have been associated with diverse disease patterns including inclusion body hepatitis, bronchitis, pulmonary congestion and oedema in different bird species.  The hydropericardium syndrome is caused by FAdV-4 in chickens mainly in Asia.  FAdV-1 (CELO), 9 and 10 are extensively studied for their potential feasibility as gene delivery vectors.

 

List of Species Demarcation Criteria in the Genus

The serologically distinguishable avian adenovirus types can be classified at least into 6 species named by the host and additional letters if more than one species exist in the same host. 

 

Species designation depends on several of the following characteristics:

·         Calculated phylogenetic distance (more than 5-10% based primarily on the distance matrix analysis of the protease, pVIII, hexon, and DNA polymerase aa sequence comparisons)

·         RFLP analysis

·         Host range

·         Pathogenicity

·         Cross-neutralization

·         Ability to recombine

For example the fowl adenovirus serotypes can be grouped into five species on the basis of RFLP profiles and the lack of significant cross-neutralization.

List of Species in the Genus

Note: A special problem that has been addressed but not resolved is the lack of consensus in the numbering of the individual serotypes.  Thus some strains deposited in American Type Culture Collection are numbered differently from those in more recent publications.  For this reason, one representative strain of each serotype is also listed (in parenthesis).

Species in the Genus

Falcon adenovirus A  
          Falcon adenovirus 1

(FaAdV-1)

Fowl adenovirus A

 

Fowl adenovirus 1 (CELO)

(FAdV-1)

Fowl adenovirus B

 

Fowl adenovirus 5 (340)

(FAdV-5)

Fowl adenovirus C

 

Fowl adenovirus 4 (KR95)

(FAdV-4)

Fowl adenovirus 10 (CFA20)

(FAdV-10)

Fowl adenovirus D

 

Fowl adenovirus 2 (P7-A)

(FAdV-2)

Fowl adenovirus 3 (75)

(FAdV-3)

Fowl adenovirus 9 (A2-A)

(FAdV-9)

Fowl adenovirus 11 (380)

(FAdV-11)

Fowl adenovirus E

 

Fowl adenovirus 6 (CR119)

(FAdV-6)

Fowl adenovirus 7 (YR36)

(FAdV-7)

Fowl adenovirus 8a (TR59)

(FAdV-8a)

Fowl adenovirus 8b (764)

(FAdV-8b)

Goose adenovirus

 

Goose adenovirus 1

(GoAdV-1)

Goose adenovirus 2

(GoAdV-2)

Goose adenovirus 3

(GoAdV-3)

Tentative Species in the Genus

Duck adenovirus B

 

Duck adenovirus 2

(DAdV-2)

Pigeon adenovirus

 

Pigeon adenovirus 1

(PiAdV)

Turkey adenovirus B

 

Turkey adenovirus 1

(TAdV-1)

Turkey adenovirus 2

(TAdV-2)

 

Genus           Atadenovirus

Type Species               Ovine adenovirus D

Distinguishing Features

Atadenoviruses are serologically distinct from viruses within other adenovirus genera and their genomic organization and capsid protein complements are also different.  Atadenoviruses have broad host range including animal species (snakes, lizards, duck, goose, chicken, possum and ruminants) from several vertebrate classes (reptilia, birds, mammals).  Virions are relatively heat stable and retain substantial infectivity after treatment for 30 min at 56°C which inactivates mastadenovirions.  A gene for a novel structural protein p32K is present at the left end of the genome.  Protein p32K is unique for atadenoviruses, and occurs in every members studied so far.  In addition, genes LH1, E4.1, and RH1–6 are unique to the genus but not present within all members.  Similarly, genes at the right end of DAdV-1 are so far unique to that virus and may be host-specific in function.  Genes LH3 and E4.3 (and its homolog, the E4.2) show limited similarity with mastadenovirus proteins E1B 55K and E4 34K, respectively.  No immunomodulatory genes such as those found in the mastadenovirus E3 region have been identified.  The genome size of sequenced isolates ranges from 29,574 (OAdV-7) to 33,213 bp (DAdV-1) with ITRs of 46 (OAdV-7) to 59 (BAdV-4) nt.  For ruminant, marsupial and avian atadenoviruses the GC content of the DNA is low and varies between 33.7 (OAdV-7) and 43% (DAdV-1).  The corresponding high AT content was deemed to be sufficiently characteristic to justify the name of the genus.  Atadenoviruses originating from reptiles seem to have a balanced G+C content.

 

Atadenoviruses have several unique proteins, and some that show very little similarity to their suspected counterparts in other adenovirus genera.

 

The central part of the genome of atadenoviruses is similar to that of mastadenoviruses (except that there is no protein V and IX genes), while the extremities of the genomes are different.  The first gene on the left-hand end of the genome is that of a novel protein p32K, which occurs only in atadenoviruses.  The right-hand end of the genome contains several genes homologous with each other.  There are two E4 34K homolog genes, and two to four RH homologs.  DAdV-1 has a unique genome region at the far right-hand end with seven uncharacterized ORFs.  ORF5 and 6 show homology to each other.  The unique region of DAdV-1 also contains a VA RNA gene seemingly homologous with that of FAdV-1.  Certain atadenoviruses can cause haemorrhagic epizooty in free-living ruminants.  DAdV-1 was also associated with a specific clinical disease of hens, characterized by sharp decrease in egg production (the egg drop syndrome) all over the world.  Several vectors have been constructed from OAdV-7 for human gene therapy purposes.

List of Species Demarcation Criteria in the Genus

Serologically distinguishable serotypes are grouped into species.  The data available at present suggest the separation of several species within the genus, but only 4 of them have been approved yet (Fig. 4).  Virus types listed as “Tentative Species in the Genus” need further study before being placed into the existing or additional species.

Species designation depends on several of the following characteristics:

·         Calculated phylogenetic distance (>5-10%)

·         Host range

·         DNA hybridization

·         Percentage of G+C in the genome

·         Cross-neutralization

·         Organization of the right-hand end of the genome

List of Species in the Genus

Species in the Genus

Bovine adenovirus D

 

Bovine adenovirus 4

(BAdV-4)

Bovine adenovirus 5

(BAdV-5)

Bovine adenovirus 8

(BAdV-8)

Bovine adenovirus - Rus

(BAdV-Rus)

Duck adenovirus A

 

Duck adenovirus 1

(DAdV-1)

(Egg drop syndrome virus)

 

Ovine adenovirus D

 

Goat adenovirus 1

(GAdV-1)

Ovine adenovirus 7

(OAdV-7)

(Ovine adenovirus isolate 287)

 

Possum adenovirus

 

Possum adenovirus 1

(PoAdV-1)

Snake adenovirus

 

Snake adenovirus 1

(SnAdV-1)

Tentative Species in the genus

Bearded dragon adenovirus

 

Bearded dragon adenovirus 1

(BDAdV-1)

Bovine adenovirus E

 

Bovine adenovirus 6

(BAdV-6)

Bovine adenovirus F

 

Bovine adenovirus 7

(BAdV-7)

Cervine adenovirus

 

Odocoileus adenovirus 1

(OdAdV-1)

(from white-tailed deer, mule deer, black-tailed deer, moose)

 

Chameleon adenovirus

 

Chameleon adenovirus 1

(ChAdV-1)

Gecko adenovirus

 

Gecko adenovirus 1

(GeAdV-1)

 

Genus           Siadenovirus

Type Species               Frog adenovirus

Distinguishing Features

Siadenoviruses are serologically distinct from members of the other adenovirus genera.  This genus comprises only three known members, Frog adenovirus 1 (FrAdV-1), Turkey adenovirus 3 (TAdV-3), and Raptor adenovirus 1 which were isolated from an amphibian (frog) and from birds (turkey, pheasant, and chicken, and birds of prey, respectively).  The genomic organization of siadenoviruses is also different.  The genes of protein V and IX are missing, as well as any homologs of mastadenovirus early regions E1, E3 and E4.  The genome of all three siadenovirus types is fully sequenced, and they represent the shortest adenovirus genomes known to date.  Their length is 26,163 and 26,263 bp, with G+C contents of 38 and 35% respectively, and with ITRs of 36 and 39 bp long, in FrAdV-1 and TAdV-3, respectively.

 

Beside the proteins conserved in all adenoviruses, there are only five ORFs supposed to code for novel proteins.  At the left-hand end of the genome, the first putative gene shows homology with sialidase genes.  Adjacent to it, is another novel ORF predicted to code for a highly hydrophobic protein.  The gene named “E3” solely because of its position between the pVIII and fiber genes is not homologous with any of the mastadenovirus E3 genes (or with any other known genes).  The right-hand end of the genome harbors ORF 7 and 8 on the opposite (l) strand (transcribed left-ward).  TAdV-3 has no common complement-fixing antigen with other adenoviruses isolated from birds and classified into the aviadenovirus or atadenovirus genera.  FrAdV-1 is supposed to be nonpathogenic.  TAdV-3 is associated with specific disease entities in different hosts (haemorrhagic enteritis in turkey, marble spleen disease in pheasants, and splenomegaly in chickens).

List of Species Demarcation Criteria in the Genus

There are only three members of the genus, and they represent clearly three different species.

Species designation depends on the following characteristics:

·         Calculated phylogenetic distance (>10%)

·         Host range

List of Species in the Genus

Species in the Genus

Frog adenovirus

 

Frog adenovirus 1

(FrAdV-1)
Raptor adenovirus A  
          Raptor adenovirus 1

(RAdV-1)

Turkey adenovirus A

 

Turkey adenovirus 3

(TAdV-3)

(turkey haemorrhagic enteritis virus, marble spleen disease virus, avian adenovirus splenomegaly virus)

 

Tentative Species in the Genus

None reported. (Or rather none is on the level to be accepted as tentative species. By the way, the level of tentative species will be diminished in the next ICTV Report as a non-official taxon.)

 

Genus           iCHTadenovirus

Type Species               Sturgeon adenovirus A

Distinguishing Features

Ichtadenoviruses are serologically distinct from members of the other adenovirus genera.  This genus comprises only a single known member, white sturgeon adenovirus 1 (WSAdV-1).  The genomic organization of this virus is also different.  The genes of protein V and IX are missing, as well as any homologs of mastadenovirus early regions E1, E3 and E4. The G+C content is balanced. The full genome is not sequenced yet, but the genome end regions seem to have novel genes with unknown function.

 

WSAdV-1 is supposed to be nonpathogenic.

List of Species in the Genus

Species in the Genus

Sturgeon adenovirus A

 

White sturgeon adenovirus 1

(WSAdV-1)

Tentative Species in the Genus

None reported.

 

 

 

Figure 2:  Phylogenetic tree of adenoviruses based on distance matrix analysis of hexon aa sequences.  (Certain sequences were combined from different partial GenBank entries and may contain short unknown parts).  The Seqboot (bootstrap), Protdist (Dayhoff PAM 001 matrix), Fitch (global rearrangements) programs of the PHYLIP 3.6 package were used, with the Consense program from PHYLIP 3.5c.  Unrooted tree; white sturgeon adenovirus was chosen as outgroup.  Adenoviruses are marked by the name of the host and the serotype number.  Species names are indicated in an abbreviated mode for graphic convenience.  Possible new species and genus names are not italicized.  Bootstrap values higher than 50 (from 100 re-samplings) are shown for every confirmed branching.

Derivation of Names

Adeno: from Greek aden, adenos, "gland"; in recognition of the fact that adenoviruses were first isolated from human adenoid tissue.

At: from English adenine and thymine, in recognition that the genome of the first recognized members of the genus (from ruminant, avian and marsupial hosts) has a remarkably high AT content.

Avi: from Latin avis, "bird".

Icht:truncated from Greek ichthys, “fish”.

Mast: from Greek mastos, "breast".

Si: from English sialidase, in recognition that members of the genus have a putative sialidase homolog.