Reverse Transcriptase

Reverse transcriptase is an RNA-directed DNA polymerase common in retroviruses. The HIV retrovirus that causes AIDS contains a reverse transcriptase. Like other RNA-dependent polymerases, reverse transcriptase is very error prone because it contains no proofreading activity. The replication scheme of retroviral RNA is as follows:

> 1. Viral RNA in the host cell base pairs with a specific tRNA molecule to provide a primer for DNA replication.

> 2. Reverse transcriptase makes DNA towards the 5' end of the viral RNA.

> 3. RNase H partially degrades RNA from the RNA-DNA duplex, removing the 5' terminus.

> 4. The 3' terminus of the viral RNA base pairs with the overhanging DNA strand, forming a circle-like structure.

> 5. Reverse transcriptase makes a DNA copy of the entire genome, using the 3' end of the DNA strand as a primer.

> 6. The RNA strand of the duplex is removed and a DNA strand complementary to the first DNA strand is synthesized to form a duplex.

> 7. The duplex integrates into the host chromosome

The drug, 3'-Azido-2'3'-dideoxythymidine (AZT), when converted to the corresponding 5' triphosphate in cells, is an inhibitor of the HIV reverse transcriptase enzyme. Other nucleoside analogs, such as 2'3'-dideoxycytidine (ddC), 2'3'-dideoxyinosine (ddI), and 2'3'-didehydro-3'-deoxythymidine (d4T) (see here) are also converted to triphosphates and act by blocking DNA chain elongation after they are incorporated into DNA.

See also: Retrovirus Replication, RNA Viruses

INTERNET LINKS:

> 1. Reverse Transcriptase

> 2. HIV Insite

> 3. General Replication Strategies for RNA Viruses

> 4. A Multimedia AIDS and HIV Resource

> 5. All the Virology on the WWW