Gene Delivery Using Viral Vectors - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 211

0 2 4 6 8 10 12 14 16 18 20th

Lysis
release

Genes

1

L5, I2, TP

E1A, E2A, E4

2

3

E2A, TP, POL

E1A, E1B

4

5

E1A, E1B

6

E1B

7

E1B, E4

V4, L4

8

E3

9

0 2 4 6 8 10 12 14 16 18 20 h

Figure 5.3 Life cycle of the adenoviral vector.

is identical to that for coxsackie B virus and is named the Coxsackie/adenovirus
receptor (CAR). After the attachment, interaction between the penton base and  v
integrins on the cell surface leads to internalization of the virus through endocytosis.
Once inside the cell, the virus escapes the endosome with the help of the penton base
and translocates to the nuclear pore complex, where the viral DNA is released into
the nucleus and transcription begins. Transcription, replication, and viral packaging
take place in the nucleus of the infected cell (adsorption and entry into the cell are
shown in Figs. 5.4 and 5.5).

1. Attachment to cell surface receptor
2. Receptor-mediated endocytosis

5.2.4.3 Transcription
Transcription of the gene occurs from both strands, and a series of complex splicing
accompanies transcription. Adenovirus transcription occurs in a two-phase event, Early
and Late. Early and Late mean before and after viral DNA replication, respectively.
The early transcribed regions are E1, E2, E3, and E4. The E1 gene products can be fur-
ther subdivided into E1A and E1B. E1 gene products are involved in the replication of
the virus. The E2 region is subdivided into E2A and E2B. These proteins provide the
machinery for viral DNA replication and the ensuing transcription of late genes. Most
of the E3 proteins are involved in modulating the immune response of infected cells, a
function not essential for viral growth in vitro . The gene products encoded by the E4
region (called ORFs 1-6/7) are involved in the metabolism of virus messenger RNA