What is Deoxyribonucleic Acid (DNA) transcription in relation to Human Immunodeficiency Virus (HIV)?

From the Guidelines

DNA Transcription in HIV

DNA transcription in the context of HIV refers to the process by which the viral genome is transcribed into RNA, which is then used to produce viral proteins and new viral particles. This process is crucial for the replication and survival of the virus [ 1 ].

Key Aspects of HIV Transcription

• Transcriptionally-competent HIV infected cells: These cells are capable of producing viral RNA transcripts and may contribute to chronic inflammation and immune activation during antiretroviral therapy (ART) [ 1 ].
• Measuring transcriptional activity: Assays that measure cell-associated HIV RNA transcripts, such as total, elongated, unspliced, polyadenylated, and multi-spliced RNA, can indicate the degree of HIV residual transcriptional activity [ 1 ].
• Importance of transcriptional activity: Levels of cell-associated HIV RNA during ART can serve as predictors of viral rebound after therapy interruption, highlighting the biological and clinical relevance of these measures [ 1 ].

Targeting HIV Transcription

The transcription process is targeted by various antiretroviral therapies, including:

• Nucleoside reverse transcriptase inhibitors (NRTIs): Such as tenofovir disoproxil fumarate and emtricitabine, which inhibit the reverse transcription of the viral RNA genome into DNA.
• Integrase strand transfer inhibitors (INSTIs): Such as raltegravir, which prevent the integration of viral DNA into the host genome.
• Assays for measuring HIV reservoir size: Prioritization of assays, such as IPDA, Q4PCR, cell-associated RNA, and inducible p24 assay, is recommended for measuring HIV reservoir size in cure-directed clinical trials [ 1 ].

Conclusion is not allowed, so the response is ended here.

From the FDA Drug Label

FTC, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate (FTC-TP), which inhibits the activity of the HIV-1 reverse transcriptase (RT) by competing with the natural substrate deoxycytidine 5'‑triphosphate and by being incorporated into nascent viral DNA resulting in chain termination

The process of Deoxyribonucleic Acid (DNA) transcription in relation to Human Immunodeficiency Virus (HIV) is not directly described in the provided drug label. However, it can be inferred that HIV uses reverse transcription, a process where the viral RNA genome is converted into DNA, to replicate itself. The drug emtricitabine works by inhibiting the reverse transcriptase enzyme, which is essential for this process.

• Key points:
  • Emtricitabine inhibits HIV-1 reverse transcriptase
  • Reverse transcriptase is necessary for HIV replication
  • Emtricitabine is incorporated into nascent viral DNA, resulting in chain termination
• Main idea: Emtricitabine works by inhibiting the reverse transcription process, which is essential for HIV replication 2

From the Research

Deoxyribonucleic Acid (DNA) Transcription in Relation to Human Immunodeficiency Virus (HIV)

• DNA transcription in the context of HIV refers to the process of reverse transcription, where the viral RNA genome is converted into a double-stranded DNA copy 3, 4.
• This process is catalyzed by the viral enzyme reverse transcriptase (RT) and is a crucial step in the HIV life cycle, as it allows the virus to integrate its genetic material into the host cell genome 3, 5.
• The reverse transcription process involves the initiation of DNA synthesis by cellular tRNALys3, which binds to the complementary primer binding site of the genomic RNA 3.
• The RT enzyme then translocates from the initially bound RNA/RNA duplex into chimeric replication intermediates and finally accommodates newly synthesized DNA/RNA hybrids 3.
• The interaction between RT and integrase (IN) is also essential for reverse transcription, with the C-terminal domain of IN binding to RT and facilitating the process 5.
• Recent studies have shown that completion of reverse transcription and viral genome uncoating occur in the nucleus, rather than in the cytoplasm, and that the cone-shaped capsid plays a crucial role in this process 6.
• The structure of an HIV-1 RT initiation complex has been determined using cryo-electron microscopy, revealing an inactive polymerase conformation with open fingers and thumb, and a nucleic acid primer-template complex shifted away from the active site 7.