Reverse transcriptase viral coded

The enzyme reverse transcriptase, as well as some other enzymes used in virus replication the gene that codes these enzymes is the pol gene. The other viral enzymes specified by the pol gene are protease and integrase. Protease is involved in muturation of viral proteins as the virus buds out from the cell, and integrase is responsible for integration of the viral DNA into the cell s chromosomal DNA. 

It has been demonstrated that the chemical steps that comprise DNA integration are carried out by the viral protein, integrase (IN). Integrase is encoded by the 3 end of the viral pol gene, which also codes for two other viral enzymes, the protease and reverse transcriptase. These three enzymes are initially synthesized as part of a larger polyprotein that is subsequently cleaved by the protease to the individual proteins. 

Inhibition of viral coded reverse transcriptase using nucleoside analogues (e.g. ddl, 3TC, d4T, AZT)... 

Fig. 14.22. Infection of a host cell by HIV. The HIV virus particle binds to the CD4 receptor and a chemokine coreceptor in the host cell membrane. The virus enters the ceU and uncoats, releasing its RNA and proteins. The viral enzyme reverse transcriptase produces a double-stranded DNA copy that is integrated into the host cell genome. HIV is now a provirus. Transcripts of the viral DNA are sphced and translated to produce the proteins Tat, Rev, and Nef. Tat stimulates transcription of the viral DNA, and Rev causes the viral RNA transcripts to leave the nucleus unsphced. The unspliced RNA serves as the viral genome and also codes for the proteins of the viral core and envelope. The envelope proteins (gp41 and gpl20, which are derived from the env protein) enter the cell membrane. The viral core proteins are S5mthesized as a polyprotein, which is cleaved by a protease as the viral particles form and bud from the ceU membrane. The particles carry membrane lipid as a coat that contains gp41 and gpl20. Nef indirectly aids in the assembly of viral particles. Pol is the reverse transcriptase produced from the viral RNA. = stimulates.

The AIDS retrovirus penetrates the T cells of the immune system (1 in Figure 17.1). Once inside, the virus releases its contents, and the reverse transcriptase of the AIDS virus translates the RNA code of the virus into double-stranded DNA (2 in Figure 17.1). The virus DNA enters the T cell nucleus and is incorporated into the cell s own DNA (3 in Figure 17.1) Then the T cell makes RNA from viral DNA, the proteins needed for a new virus are made from this RNA (4 in Figure 17.1), and the new virus is released (5 in Figure 17.1). Eventually the T cell swells and dies, releasing more AIDS viruses to attack other T cells. As their T cells are destroyed, individuals are attacked by diseases that are normally defeated by the body s immune system and thus are rare in healthy individuals. 

Complementary DNA Synthesis.—In 1970 it was established that the RNA tumour viruses replicate, via a DNA intermediate, employing an enzyme coded for by the viral genome. -The enzyme, RNA-dependent DNA polymerase (E.C. 2.1.1.1.), popularly known as reverse transcriptase, proved to have low specificity and to be able to transcribe efficiently and faithfully any RNA into a complementary DNA (cDNA), provided a preformed primer was available to initiate transcription (for a review, see ref. 16). By use of this enzyme it was possible to synthesize in vitro highly radioactive DNA complementary to isolated messenger RNAs. 

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