Retroviruses retroviral genome

Some 24 per cent of all gene therapy clinical trials undertaken to date have employed retroviral vectors as gene delivery systems. Retroviruses are enveloped viruses. Their genome consists of ssRNA of approximately 5-8 kb. Upon entry into sensitive cells, the viral RNA is reverse transcribed and eventually yields double-stranded DNA. This subsequently integrates into the host cell genome (Box 14.1). The basic retroviral genome contains a minimum of three structural genes ... 

The first clue that cells could be transformed by defects in normal genes came from studies of the composite retroviruses. Although this class of animal retroviruses have not been linked to human cancer, cell-culture studies demonstrated that the retroviral genome encoded all the information required for cell transformation. 

Retroviruses of vertebrates are, perhaps, the most widely studied class of eukaryotic transposable elements. These RNA viruses use reverse transcriptase to synthesize a circular duplex DNA, which can integrate into many sites of the host cell chromosome. The integrated retroviral genome bears remarkable resemblance to a bacterial composite transposon (compare Figure 25.38 with Figure 25.35). 

Retroviruses R Us the retroviral inheritance of the human race. Retroviruses R Us was the title of the author s presentation given at the Kaposi Foundation s Award Conference in Budapest, Hungary (2010, vide infra). Ancient deposits of retroviral genomic repetitive elements (LTRs) occupy some 40 % of the human genome. 

Figure 14.4 Schematic representation of (a) the proviral genome of a basic retrovirus and (b) the genome of a basic engineered retroviral vector carrying the gene of interest. Refer to text for further details...

Some well-characterized eukaryotic DNA transposons from sources as diverse as yeast and fruit flies have a structure very similar to that of retroviruses these are sometimes called retrotransposons (Fig. 26-33). Retro-transposons encode an enzyme homologous to the retroviral reverse transcriptase, and their coding regions are flanked by LTR sequences. They transpose from one position to another in the cellular genome by means of an RNA intermediate, using reverse transcriptase to make a DNA copy of the RNA, followed by integration of the DNA at a new site. Most transposons in eukaryotes use this mechanism for transposition, distinguishing them from bacterial transposons, which move as DNA directly from one chromosomal location to another (see Fig. 25-43). 

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