Changes

Adenoviruses enter the host cell by means of interaction of the receptor, coxsackievirus adenovirus receptor (CAR), with a domain on the fibre protein called the knob domain. Some reports suggest that MHC molecules and sialic acid residues may also function as adenovirus receptors. This initial interaction is followed by a secondary interaction where a motif in the penton protein interacts with αv integrin, stimulating endocytosis of the adenovirus via clathrin-coated pits. Once inside the cell the endosome acidifies, causing the caspid components of the adenovirus to dissociate and releasing the virion into the cytoplasm. The virus is then transported by the microtubule netwoek to the nuclear pore complex, where the adenovirus particle disassembles and DNA enters the nucleus. Viral DNA associates with histone proteins, and replication begins.

Adenoviruses enter the host cell by means of interaction of the receptor, coxsackievirus adenovirus receptor (CAR), with a domain on the fibre protein called the knob domain. Some reports suggest that MHC molecules and sialic acid residues may also function as adenovirus receptors. This initial interaction is followed by a secondary interaction where a motif in the penton protein interacts with αv integrin, stimulating endocytosis of the adenovirus via clathrin-coated pits. Once inside the cell the endosome acidifies, causing the caspid components of the adenovirus to dissociate and releasing the virion into the cytoplasm. The virus is then transported by the microtubule netwoek to the nuclear pore complex, where the adenovirus particle disassembles and DNA enters the nucleus. Viral DNA associates with histone proteins, and replication begins.

The adenovirus life cycle is separated, by the DNA replication process, into two phases: an early and a late phase. In both phases a primary transcript is generated which is alternatively spliced to generate monocistronic mRNAs compatible with the host’s ribosome, allowing for the products to be translated.

The virus replication process is divided to the early and late phases, which are separated by DNA replication. Genes transcribed in the early phase are are responsible for producing non-structural, regulatory proteins. These regulatory proteins control the expression of host proteins necessary for DNA synthesis, activate other virus genes and help prevent death of the infected cell by host immune defences. Once the early genes prepared virus proteins, replication machinery and replication substrates, the adenovirus genome is able to replicate. A protein covalently bound to the 5’ end of the adenovirus genome acts as a primer, and the viral DNA polymerase then uses a strand displacement mechanism for replication. The late phase of the adenovirus life cycle produces structural proteins in which to pack the new genetic material. The virus can then be release from the cell by lysis.

 

The early genes are responsible for expressing mainly non-structural, regulatory proteins. The goal of these proteins is threefold: to alter the expression of host proteins that are necessary for DNA synthesis; to activate other virus genes (such as the virus-encoded DNA polymerase); and to avoid premature death of the infected cell by the host-immune defenses (blockage of apoptosis, blockage of interferon activity, and blockage of MHC class I translocation and expression).

 

 

DNA replication separates the early and late phases. Once the early genes have liberated adequate virus proteins, replication machinery and replication substrates, replication of the adenovirus genome can occur. A terminal protein that is covalently bound to the 5’ end of the adenovirus genome acts as a primer for replication. The viral DNA polymerase then uses a strand displacement mechanism, as opposed to the conventional Okazaki fragments used in mammalian DNA replication, to replicate the genome.

 

The late phase of the adenovirus life cycle is focused on producing sufficient quantities of structural protein to pack all the genetic material produced by DNA replication. Once the viral components have successfully been replicated the virus is assembled into its protein shells and released from the cell as a result of virally induced cell lysis.

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