What is the mechanism of action of reverse transcriptase (RT) in viral replication?

From the Guidelines

The mechanism of action of reverse transcriptase (RT) in viral replication involves the conversion of viral RNA into viral DNA through a process known as reverse transcription, which is crucial for the replication of retroviruses like HIV.

Key Steps in Reverse Transcription

• The reverse transcriptase enzyme catalyzes the synthesis of a complementary DNA (cDNA) copy from the viral RNA template 1.
• This cDNA copy is then elongated to form a double-stranded DNA molecule, which is a critical step in the viral replication cycle.

Role of Reverse Transcriptase in Viral Replication

The process of reverse transcription is essential for the replication of retroviruses, including HIV, as it allows the viral genome to be converted into a form that can be integrated into the host cell's DNA 1.

Inhibition of Reverse Transcriptase

Antiretroviral medications, such as zidovudine and nevirapine, target reverse transcriptase activity and prevent viral DNA elongation, thereby inhibiting viral replication 1.

Mutations and Resistance

Mutations in the reverse transcriptase gene, such as the N348I mutation, can confer resistance to antiretroviral medications by altering the enzyme's activity or reducing the efficiency of RNase H cleavage 1.

Clinical Implications

Understanding the mechanism of action of reverse transcriptase and the development of resistance mutations is crucial for the effective management of HIV infection and the development of new antiretroviral therapies 1.

From the FDA Drug Label

The principal mode of action of ZDV-TP is inhibition of reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue The principal mode of action of 3TC-TP is inhibition of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue

The mechanism of action of reverse transcriptase (RT) in viral replication is inhibition by nucleoside analogues such as zidovudine and lamivudine. These analogues are phosphorylated to their active triphosphate metabolites, which are then incorporated into the viral DNA, causing DNA chain termination. This prevents the virus from replicating.

• Key points:
  • Reverse transcriptase is an enzyme that plays a crucial role in viral replication
  • Nucleoside analogues such as zidovudine and lamivudine inhibit reverse transcriptase
  • Inhibition occurs through DNA chain termination after incorporation of the nucleotide analogue 2 3

From the Research

Mechanism of Action of Reverse Transcriptase (RT)

The mechanism of action of reverse transcriptase (RT) in viral replication involves the conversion of single-stranded RNA into double-stranded DNA. This process is catalyzed by the RT enzyme, which has two main activities:

• DNA polymerase activity: synthesizes DNA using RNA or DNA as templates 4, 5
• Ribonuclease H activity: degrades RNA when forming RNA/DNA hybrids 4, 5

Key Steps in Reverse Transcription

The key steps in reverse transcription include:

• Initiation of minus-strand DNA synthesis: RT uses a primer to initiate DNA synthesis on the viral RNA template 6
• Synthesis of minus-strand DNA: RT extends the primer to produce a complementary DNA copy of the viral RNA 6
• Degradation of RNA template: RT-associated RNaseH activity degrades the genomic RNA template 4, 6
• Synthesis of plus-strand DNA: RT uses a primer to initiate DNA synthesis on the minus-strand DNA template 7, 6

Inhibition of Reverse Transcription

Reverse transcription can be inhibited by various mechanisms, including:

• Triple-helix forming oligonucleotides: can bind to the viral RNA and prevent RT from accessing the template 7
• RT inhibitors: can bind to the RT enzyme and prevent it from catalyzing DNA synthesis 4, 5
• RNaseH inhibitors: can prevent the degradation of the RNA template and inhibit the synthesis of plus-strand DNA 4