Molecular Biology

There once was a virus named adeno

and to the intestine it'll go 

it'll make you feel bad

and your tummy feel mad

so out to the bathroom you'll go!

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Virus Structure

Viral Morphology:

Adenoviruses are naked (non-enveloped) viruses with a relatively simple construction. The nucleocapsid presents icosahedral symmetry with a triangulation number, T=25. On the surface of the capsid there are projections of filaments, which stick out from each of the 12 vertices of the icosahedral shape giving adenovirus its distinctive shape.

  

Genome:

The genome consists of one segment of double-stranded DNA about 36,000 nucleotides long and linear. Within the genome are inverted terminal repetitions (ITR), which are redundant sequences of bases found at each end. There is also a 5' protein which is virally encoded and linked covalently to the 5' end of each strand of the DNA. This 5' protein serves as a primer during viral replication, which occurs in the nucleus of the host cell. 

Viral Replication 

Transcription of the mRNAs:

Transcription is regulated by  virus-encoded trans-acting regulatory factors and the DNA molecule serves as a template in the synthesis of the precursor mRNA. Both strands of the double-stranded DNA adenovirus genome encode genes. The products of the immediate early genes are actually used to regulate the expression of the rest of the early genes. 

The initial mRNA contains exon and intron sequences. Each gene is capable of making multiple protein products because of alternative splicing mechanism of the mRNA transcript. In fact, the mechanism of gene splicing was first discovered in Adenoviruses by Phillip Sharp and Richard Roberts (who were awarded a Nobel Prize for their discovery in 1993). The mature mRNA, consequently contains only exon sequences. The intron sequences (pictured below: A, B, and C) are spliced out and the exons are joined together.


Proteins:

The adenovirus genome encodes about 30 proteins. Nonstructural proteins include: e1a, required for replication, e2b, a poly-functional protein that regulates late gene expression in the N terminus and modulates DNA synthesis in the C terminus, as well as its own DNA-dependent DNA polymerase.  At least 10 structural proteins are encoded, including capsid, core and fiber proteins.

Replication of the Viral DNA:

Replication of the adenovirus genome is generally outlined into two phases, the EARLY and the LATE phase, with the late phase characterizing DNA replication. Proteins from the E2 region of the transcript are involved in the replication of the viral DNA and include a DNA polymerase, which is  a single-stranded DNA-binding protein. Each end of the adenovirus genome contains a ITR, as previously mentioned, and DNA synthesis begins at one of the two ends with the terminal protein precursor serving as a primer. 

After the first round of replication, the product is a double-stranded genome as well as a single-stranded copy of one of the original genome strands, which serves as a single-stranded DNA on which DNA synthesis can begin. It is copied, finally producing two copies of  the double-stranded adenovirus genome.

Assembly and Release:

Progeny virions are assembled in the nucleus of the host cell. The viral protease, which adenoviruses encode, cleaves four viral proteins, stabilizing the viral progeny and the viral DNA contains a packaging signal towards its left end. As the adenovirus infection cycle is lytic, the host cell eventually dies due to infection.

Immune System Evasion:

Adenoviruses are able to avoid the immune system in several ways allowing them to infect the host more successfully. One way in which this occurs is that the E1b protein inhibits apoptosis of the host cell, therefore allowing more progeny to be made before the cell dies. Also, the E3 gene encodes a protein that blocks the host's MHC immune response. Lastly, adenoviruses have a mechanism that block interferon through virally-associated RNA.