# Büşra ZEYBEK - ADENOVIRUSES

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# Adenoviruses
***Family:*** Adenoviridae ***Genus:*** Adenoviruse ***Species:*** Human AdV-C5

* The term "adeno" is derived from Greek word meaning "spring".
* Their Classification of Baltimore is Class 1.

| Host | Diseases |
| ----------- | ----------------------- |
| Human | Respiratory Infection |
| Reptiles | Gastroenteritis |
|Mice | Epidemic Conjunctivitis |
| Vertebrates | Tumor |

**THE VIRION AND GENOME STRUCTURE**
* The adenovirus particle is a spherical capsid with 12 fibers, which project outward.
* Nonenveloped capsid
* Icosahedral Symmetry (T=25)
* ~ 150 nm diameter
* The viral genome : 35 kb, Linear-dsDNA

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**The Human Adenoviruses**
More than 60 human adenovirus subtypes have been found, divided into six subgroups designated A-G. Since subtype 5 (HAdV-C5) causes respiratory tract infection in humans, it has been extensively studied as a prototype.


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# **THE LIFE CYCLE OF ADENOVIRUS**
### **Genome**

### **Attachment and Entry**

### **Transcription and Translation**
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Early gene transcription occurs before the onset of viral genome replication. It takes place in two steps: these are appropriately termed "immediate early genes" and "early genes".
* E1A proteins play a central role in early transcription and act as a transcriptional transactivator of E2 gene transcription.
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Two early proteins E1A and E2 trigger the switch from early phase and late phase. E1A triggers the switch from immediate early to early phase by transactivation of early genes (E2, E3, and E4). E2 gene encodes three viral proteins contributing to the viral genome replication:
(1) Ad polymerase,
(2) pre-TP,
(3) DBP.
E2 proteins induce not only the viral DNA replication but also simultaneously the switch from early to late phase.
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### **Early Phase and Late Phase**



### **Genome Replication**


### **Packaging and Assembly**

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The viral capsids are assembled in the nucleus and become released from the cell by cell lysis. One E3 gene product, namely E3-11.6K, is known to be involved in cell death and virion release.
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In addition, adenoviruses are utilized as a gene therapy vector.
Adenovirus is a DNA virus, having a 35 kb DNA genome possessing over 50 genes. Due to its large genome, only the subset of genes needs to be replaced by a therapeutic gene. Thus, unlike retrovirus vector, adenovirus vector still keeps the bulk of the virus genes. For instance, in an adenovirus vector, an essential E1 gene is replaced by a transgene. This adenovirus vector should be produced in cells (ie, HEK293 cell) that stably express E1 protein. A recombinant adenovirus produced will express the therapeutic gene following entry to target cells. However, in the target cell, the adenovirus will not replicate due to the lack of the E1 gene. The above-described adenovirus vector lacking the E1 gene is often called the “first-generation adenovirus vector.” One flaw of the first-generation vector is that replication-competent recombinant adenovirus, although low level, is produced. To obviate this drawback, subsequently, the so-called second-generation adenovirus vector was created, which lacks not only the E1 gene but also the E2 and E4 genes. Eventually, to preclude the generation of the replication-competent recombinant viruses, the so-called third-generation adenovirus vector that keeps only the inverted terminal repeats (ITR) at both ends of the viral genome but lacks the entire coding region was generated.
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