Adenovirus Replication

Adenoviruses have double stranded linear DNA. The basic proteins are virally coded, but do not use cellular histones to coat their viral DNA. They are icosahedral with fibers at the intersections. The genome is approximately seven times larger than the polyoma virus genome.  This article explains adenovirus replication in detail below.

Epithelial cells are the main target of adenoviridae. When the fibers bind to the receptors in the cell surface endocytosis engulfs the virus, which is then capable of disintegrating the endosomes. Uncoating of the cell occurs, and DNA is released into the nucleus, perhaps from a nuclear pore.

Cell host RNA polymerase as well as mRNAs are incorporated from random regions of both strands that the adenovirus uses. Multiple transcription promoters mean more flexible control, and mRNA material is processed via polyadenylation, cell capping, methylation and even at times by splicing enzyme processes, which are then sent to the cytoplasm and translated as adenovirus. No section of the icosahedral virion contains all of the components, but each promoter makes primary transcripts which undergo alternative splicing.

The early proteins in this process are those which are needed for transcription, such as the E1A protein that is used in transcribing the other early genes. While E1A is considered an “immediate” early gene, the other genes are often called “delayed” early genes.

The early proteins are also needed for DNA synthesis of the adenovirus, and this includes DNA polymerase. The proteins that alter host cell gene expressions are also necessary. This would include those genes with products that directly interfere with the host’s cell cycle regulation, or its anti-viral response, or both.

In the late phase of DNA adenovirus replication DNA polymerase is encoded from the adenovirus. A strand displacement system replicates the DNA. The strands are synthesized continuously without Okazaki fragments. DNA polymerases need a primer, as they are not capable of initiating synthesis. The terminal protein, which is virally coded, serves as the primer. It is covalently linked to the 5′ end of DNA strands in all adenovirus.

Switching on of the late transcription in adenovirus is not well understood at this time. The predominant coding for late mRNA is for structural proteins, though there is one late promoter. The primary transcript generates various monocistronic mRNAs.

Two types of cleavage characterize primary transcript. The first is to generate 3′ ends which undergo polyadenylation, and the second is for intron removal. How this process is controlled to produce the correct amount of each mRNA is not understood at this time. The virus seems to make an excess of mRNA and proteins, indicating that exact control may not be necessary to the process.

Adenovirus particles are assembled in the nucleus. Capsids are formed before the DNA enters the particles, after which the capsids mature and the cells lyse and leak virions. Since more structural proteins were made than needed the excess accumulate in the nucleus to form inclusion bodies.

In summary, adenoviruses are more complex and larger than papovaviruses. Although they code their own polymerase and DNA packaging protein they also use host processes as well as viral proteins for DNA replication. Since they use RNA polymerase and RNA modification, nucleic acid synthesis takes place in the nucleus.