Adenoviridae

Properties of Adenoviridae 306

Pathogenesis and Immunity 309

Clinical Syndromes 310

Laboratory Diagnosis 312

Control 314

Further Reading 315

In 1953 Rowe and colleagues, having observed that certain explanl cultures of human adenoids spontaneously degenerated, isolated a new infectious agent which became known as "adenovirus." Before long, it became evident not only that adenoviruses may persist for years as latent infections of lymphoid I issues, but also that they are a significant cause of disease in the respiratory tract and (he eye. Subsequently, certain serotypes were found to infect the genitourinary tract, whereas more recently discovered adenoviruses have been associated with gastroenteritis or with infections of immunocompromised patients (e.g., in AIDS).

Following the discovery that certain human adenoviruses produce malignant tumors in baby rodents, some of the world's most capable molecular biologists turned their attention to the biochemistry of adenovirus replication and oncogenesis. Although it later became clear that adenoviruses play no role in human cancer, the spin-olf from this research had a major impact on our understanding of the expression of mammalian as well as viral genes. To cite just three examples, adenovirologists discovered the phenomenon of splicing of RNA transcripts, were the first to describe the role of proteins as primers for initiation of DNA replication, and pioneered techniques for elucidating the regulation of transcription programs in mammalian cells.

Properties of Adenoviridae

The family Adenovindac is defined by the properties listed in Table 19-1. The virion is a perfect icosahedron (Fig. 19-1B and 1-1 A). The outer capsid, about

Table 19-1

Properties of AdeiwvtndtK

Onus Mrtsfrtifr'JKiT'rrrfs comprises .ill 47 human serotypes

Icosahedral virion, 80-9(1 rati, 252 capsomers, 12 fibers at vertices, 12 structural proteins Linear, dsDNA genome, 36-38 kbp, inverted hTmm.il repeals, protein primer at each 5' terminus Complex program of transcription from seven early, intermediate, and late piomoters, splicing Transcription, DNA replication, and virion assembly occur in nuileus

80 nm in diameter, is composed of two main types of capsomers- 240 "hex-ons" make up the 20 triangular faces of the icosahedron, while 12 "pentons" form the 12 vertices (Fig. 1-2A). From each penlon protrudes a "fiber," giving the virion the appearance of a communications satellite (Fig. 19-1A). The genome, which is associated with an inner protein core, consists of a single linear molecule of dsDNA, 36-38 kbp in size for mammalian adenoviruses.

Capsomer Icosahedral Virus

Fig. 19-1 Adcmnuridac- (A, C) Negatively stained preparations (A) Virion showing fibers projecting from the vertices (B) Virion showing icosahedral army of capsomers Capsomers at the vertices (pentons) are surrounded by five nearest neighbors, all the others (hexons) by six. fC) Section showing crystalline army of mature virions 111 the nucleus of a human fibroblast cell Bar, lOOnm | A and H, From R. C Valentine and H G Periera, / Mol lhol 13, 13 (1965); C, courlosy Dr A K. Harrison |

Fig. 19-1 Adcmnuridac- (A, C) Negatively stained preparations (A) Virion showing fibers projecting from the vertices (B) Virion showing icosahedral army of capsomers Capsomers at the vertices (pentons) are surrounded by five nearest neighbors, all the others (hexons) by six. fC) Section showing crystalline army of mature virions 111 the nucleus of a human fibroblast cell Bar, lOOnm | A and H, From R. C Valentine and H G Periera, / Mol lhol 13, 13 (1965); C, courlosy Dr A K. Harrison |

with inverted terminal lepelitions. The DNA, in association with a 55K protein which is covalently linked lo each 5' terminus, is infectious when trans-fected into susceptible cells.

Classification

Mammalian and avian adenoviruses comprise two distinct genera, designated Masfadenovirits and Avindemmrus respectively. In turn, the genus Mas-tadciwvirus comprises numerous adenovirus serotypes specific for particular mammalian species. Currently, 47 serotypes of human adenovirus (sometimes designated h-Adl to h-Ad47) are recognized They are assigned to six subgenera (A-F) on the basis of various biochemical and serological criteria which generally match up quite well with previous assignments on the basis of certain biological characteristics, notably oncogenicity and hemagglutination (Table 19-2) Members of subgenus A were found to be highly oncogenic for baby rodents and subgenus B less so, and the six subgenera are also compatible with the earlier subdivision based on agglutination of rat or monkey red cells and with the degree of homology of the genomes.

Designation as a distinct serotype is based on a serological difference (of >16-fold) in reciprocal neutralization assays. The fiber protein is responsible for hemagglutination and is type-specific, whereas the hexon protein carries genus-specific, subgenus-specific, intertype-specific, and type-specific epitopes and, like the fiber, elicits neutralizing antibodies. Numerous isolates from AIDS patients have proved difficult to type, as they share epitopes with the fiber and/or hexon proteins of one or more distinct serotypes. Nucleic acid sequencing should reveal whether these so-called intermediate strains have arisen by mutation or by recombination.

Viral Replication

Adenoviruses bind to the host cell receptor via the fiber and enter the cell by endocytosis. The outer capsid is then removed, and the core comprising the viral genome with its associated histones enters the nucleus where mRNA transcription, viral DNA replication, and assembly of virions occur. In the nucleus the genome is transcribed by cellular RNA polymerase II according to a complex program involving both DNA strands (see Chapter 3). Products of the El A region are required to up-regulate transcription of other regions of

Table 19-2

Classification of Human Adenovmiscs

Subgenus

Serotypes

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