Taxonomic Structure of the Family
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Adenoviridae |
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Genus |
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Genus |
Virions are non-enveloped, 70-90 nm in diameter and exhibit icosahedral symmetry. Capsids have 240 non-vertex capsomers (hexons), 8-10 nm in diameter, and 12 vertex capsomers (pentons) each with one or two fibers protruding from the virion surface (Fig. 1). The length of fibers so far examined ranges between 9 and 77.5 nm. The 240 hexons are formed by the interaction of three identical polypeptides (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 together and form a protein shell that protects the inner components. The positions of hexons (II), penton bases (III), fibers (IV), and protein IX (missing from aviadenoviruses and from all studied unassigned viruses) are well established. Twelve copies of polypeptides IX are found between 9 hexons in the center of each facet. The positions of proteins IIIa, VI, and VIII are tentatively assigned. Two monomers of IIIa penetrate the hexon capsid at the edge of each facet. Multiple copies of VI form a ring underneath the peripentonal hexons. The 12 penton bases are each formed by the interaction of five polypeptides (III) and are tightly associated with one or two fibers each consisting of three polypeptides (IV) that interact to form a shaft of characteristic length with a distal knob. The 12 pentons (III and IV) are less tightly associated with the neighboring (peripentonal) hexons. Polypeptide VIII has been assigned to the inner surface of the hexon capsid. Other polypeptides (monomers of IIIa, trimers of IX, and multimers of VI) are in contact with hexons completing a continuous protein shell. Polypeptides VI and VIII appear to link the capsid to the virus core. The core consists of the DNA genome complexed with four polypeptides (V, VII, X, terminal).
Physicochemical and Physical Properties
Virion Mr is 150-180 106; buoyant density in CsCl is 1.30-1.37 g/cm3. Viruses are stable on storage in the frozen state. They are stable to mild acid and insensitive to lipid solvents. Virus infectivity is inactivated after heating at 56°C for more than 10 minutes.
Virions contain a single linear molecule of dsDNA of size between approximately 26 and 45 kbp. A virus-coded terminal protein is covalently linked to the 5-end of each DNA strand. The genome of Human adenovirus 2 (HAdV-2) comprises 35,937 bp and contains an inverted terminal repetition (ITR) of 103 bp. ITRs of 43-369 bp have been found in all viruses so far analyzed. The G+C content of DNA varies between 34 and 60%.
About 40 different polypeptides are derived from the genome - mostly via complex splicing mechanisms (Fig. 2). Almost a third of these provide structural proteins as in Figure 1. In general terms, the early gene products facilitate extensive modulation of the host cell’s transcriptional machinery (E1 and E4), assemble the virus DNA replication complex (E2) and provide means for subverting host defence mechanisms (E3). Intermediate and late gene products (L1-L5) are concerned with the assembly and maturation of the virion.
None reported.
Fiber proteins and some of the non-structural proteins are glycosylated.
Genome Organization and Replication
Virus entry is by attachment via the fiber knob to different receptors on the surface of susceptible cells, and subsequent internalisation by the interaction between the penton base and cellular v integrins. After uncoating, the virus core is delivered to the nucleus which is the site of mRNA transcription, virus DNA replication and assembly. Virus infection mediates the early shut-down of host DNA synthesis and, later, host RNA and protein synthesis. Transcription by the host RNA polymerase II involves both DNA strands and initiates (in HAdV-2) from five early (E1A, E1B, E2, E3, and E4), two intermediate, and one major late (L) promoter in a pattern as shown in Fig. 2. All primary transcripts are capped and polyadenylated. There are complex splicing patterns to produce families of mRNAs. In primate and monkey adenoviruses there are usually one or two VA RNA genes which are transcribed by cellular RNA polymerase III and these encode RNA products which facilitate translation of late mRNAs. Such VA RNA genes could not be identified in most adenoviruses. In some fowl adenoviruses the existence of one non-homologous VA RNA gene located at a different genome position has been described.
There are many non-structural proteins in addition to the structural proteins (Table 1). A number of polypeptides are modified by phosphorylation, some by glycosylation. Proteolysis of some structural polypeptides by the virus-coded protease is an essential prerequisite for virion maturation (Table 1). DNA replication is by strand-displacement using a protein priming mechanism (terminal protein) together with a virus-coded DNA polymerase and DNA-binding protein in concert with cellular factors. Virions are assembled in the nucleus sometimes in paracrystalline arrays along with similar arrays of virus structural proteins. Release is achieved following disintegration of the host cell.
Adenovirus serotypes are differentiated on the basis of neutralization assays. A serotype is defined as one which either exhibits no cross-reaction with others, or shows an 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 or biochemical differences exist. Antigens at the surface of the virion are mainly type-specific. Hexons are involved in neutralization, fibers in neutralization and hemagglutination-inhibition. Soluble antigens associated with virus infections include surplus capsid proteins which have not been assembled. As defined with monoclonal antibodies, hexons and other soluble antigens carry numerous epitopes, some that are genus-specific, others that are type-specific and others that group viruses within the genus. Free hexon protein mainly reacts as a genus-specific antigen. The hexon genus-specific antigen is located on the basal surface of the hexon, whereas hexon serotype-specific antigens are located mainly on the tower region of the hexon.
The natural host range of adenoviruses is mostly confined to one species, or to closely related species. This also applies for cell cultures. Some human adenoviruses cause productive infection in rodent cells but with low efficiency. Several viruses cause tumors in newborn hosts of heterologous species. Subclinical infections are frequent in various virus-host systems. Direct or indirect transmission occurs from throat, feces, eye, or urine, depending on the virus serotype. Human adenovirus infections are mostly asymptomatic but can be associated with diseases of the respiratory, ocular and gastrointestinal systems. Human adenovirus types 1-3, 5-7 cause respiratory infections in children. Enteric infection, as indicated by fecal shedding, is predominant in all serotypes. Human adenovirus types 40 and 41 can be isolated in high yield from feces of young children with acute gastroenteritis and are second only to rotaviruses as a major cause of infantile viral diarrhea. Human adenovirus 11 is associated with hemorrhagic cystitis. Canine adenoviruses are responsible for hepatitis as well as respiratory disease and have caused epizootic in foxes, bears, wolves, coyotes, and skunks. Avian adenoviruses have been associated with diverse disease patterns e.g., inclusion body hepatitis, hydropericardium syndrome, hemorrhagic enteritis, “marble spleen” disease, egg drop syndrome, bronchitis, pulmonary congestion and oedema. Adenoviruses infecting susceptible cells cause similar gross pathology e.g., early rounding of cells and aggregation or lysis of chromatin followed by the later appearance of characteristic basophilic or eosinophilic nuclear inclusions.
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