Gag-pol gene

During the later stages of the HIV growth cycle, the Gag and Gag-Pol gene products are translated into polyproteins, and these become immature budding particles. 

Kotsopoulou E, Kim VN, Kingsman AJ, Kingsman SM, Mitrophanous KA. 2000. A Rev-independent human immunodeficiency virus type 1 (HlV-l)-based vector that exploits a codon-optimized HIV-1 gag-pol gene. J. Virol. 74 4839-52... 

The reverse transcriptase enzyme (RT) is the primary enzyme responsible for the conversion of the viral single-strand RNA to the double-strand DNA. The reverse transcriptase enzyme is a component of the virion and is encoded by the pol gene. The RT is manufactured in the HIV-infected cells as a gag-pol fusion polyprotein. The RT is not the only enzyme necessary for the translation of RNA to DNA. The other enzymes for this conversion include RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H (Gilboa and Mitra, 1978 Prasad and Gogg, 1990). The reverse transcriptase enzyme has a high error rate (1 in 2000 bases), which produces higher incidents of mutation. Some of these mutations make the virus resistant to NNRTI treatment. 

The protease inhibitors are used in the multidrug therapy of HIV infection. Resistance to the HIV protease inhibitors results from mutations in the protease gene and perhaps the cleavage sites of gag-pol. Although different protease mutations tend to be associated with resistance to individual drugs, resistance to one protease inhibitor is often associated with a less than optimal response to other agents of this class. Indinavir, ritonavir, and lopinavir require more mutations to lose their effectiveness than do the other protease inhibitors. 

Figure 4.7. a schematic presentation of the role of protease in processing of HIV gag (structural protein) and polymerase pol essential for producing infectious virus. With inactive HIV protease, the virus generated is immature and hence not infectious. The i indicates where HIV protease cleavage occurs in producing the pol gene product essential for viral replication. 

The gag, pol, and env genes of the retroviral genome, required for retroviral replication and assembly of viral particles, can be replaced with foreign DNA. To assemble viruses that contain the recombinant genetic information, researchers must introduce the DNA into cultured cells that are simultaneously infected with a helper virus that has the genes to produce viral particles but lacks the [Pg.334]

One of the best-documented examples occurs in translation of the mRNA for the overlapping gag and pol genes of the Rous sarcoma virus (see Fig. 26-31). The reading frame for pol is offset to the left by one base pair (—1 reading frame) relative to the reading frame for gag (Fig. 1). 

The product of the pol gene (reverse transcriptase) is translated as a larger polyprotein, on the same mRNA that is used for the gag protein alone (see Fig. 26-30). The polyprotein, or gag-pol protein, is then trimmed to the mature reverse transcriptase by proteolytic digestion. Production of the polyprotein requires a translational frameshift in the overlap region to allow the ribosome to bypass the UAG termination codon at the end of the gag gene (shaded pink in Fig. 1). 

There are two classes of retrotrotransposons those with long terminal repeats (LTRs) and those without (LTRs). The first group is closely related to retroviruses, but its members lack genes for envelope proteins. They do carry gag and pol genes similar to those of retroviruses (Fig. 28-3). Most retrotransposons are defective and do not move. Over evolutionary time they accumulate in the genome, sometimes to the extent that the genome size grows enormously. This... 

Fig. 10. The structure of mouse DNA containing the integrated mouse mammary tumour provirus. The integrated viral DNA can be present in many copies. The provirus contains two long terminal repeat sequences, LTR, only one of which (left) is shown in detail here. Each LTR contains sequences termed U3, R and U5 (for details, see Ref. 67). Interspersed between the LTRs are the genes named gag, pol and env, encoding viral coat proteins, reverse transcriptase and envelope proteins, respectively. The glucocorticoid-binding sequence is represented by the black box, and the transcriptional initiation area is indicated by the hatched box.

Many retrotransposons encode proteins that are homologous with the gag and pol genes of retroviruses.23 Because the function of the reverse transcriptase enzyme may be necessary for the transposition of these elements, it is important to search for sequence similarities in the repetitive elements that are newly isolated. 

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