Iithe Adenovirus

The adenovirus (Ad) has a nonenveloped icosohedral capsid containing a linear double-stranded DNA genome of —30-40 kilobase (kb). Of the —50 serotypes of human Ad, the most extensively characterized are serotypes 2 (Ad2) and 5 (Ad5) of subgroup C [reviewed in (1)]. The 36-kb genomes of Ad2 and Ad5 are flanked by inverted terminal repeats (ITRs), which are the only sequences required in cis for viral DNA replication. A cis-acting packaging signal, required for encap-sidation of the genome, is located near the left ITR (relative to the conventional map of Ad). The Ad genome can be roughly divided into 2 sets of genes (Fig. 1): the early region genes, E1A, E1B, E2, E3, and E4, are expressed before DNA replication; and the late region genes, L1 to L5, are expressed to high levels after initiation of DNA replication. The E1A transcription unit encodes 2 major E1A proteins that are involved in transcriptional regulation of the virus and stimulation of the host cell to enter an S-phase-like state and is the first early region to be expressed during viral infection. The two major E1B proteins are necessary for blocking host mRNA transport, stimulating viral mRNA transport, and blocking E1A-induced apoptosis. The E2 region encodes proteins required for viral DNA replication and can be divided into two subregions; E2a encodes the 72-kD DNA-binding protein and E2b encodes the viral DNA polymerase and terminal protein precursor (pTP). The E3 region, which is dispensable for virus growth in cell culture, encodes at least 7 proteins, most of which are involved in host immune evasion. The E4 region encodes at least 6 proteins, some functioning to facilitate DNA replication, enhance late gene expression, and decrease host protein synthesis. The late region genes are expressed from a common major late promoter (MLP) and are generated by alternative splicing of a single transcript. Most of the late mRNAs encode virion structural proteins. In addition to the early and late region genes, 4 other small transcripts are also produced. The gene-encoding protein IX (pIX) is colinear with E1B but uses a different promoter and is expressed at an intermediate time, as is the pIVa2 gene. Other late transcripts include the RNA polymerase III-transcribed VA RNA I and II.

Virus infection is initiated through the Ad fiber protein binding to the primary coxsackie-adenovirus receptors (CAR)

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