Reverse Transcription of Retroviruses and LTR Retrotransposons

Abstract

The enzyme reverse transcriptase (RT) was discovered in retroviruses almost 50 years ago. The demonstration that other types of viruses, and what are now called retrotransposons, also replicated using an enzyme that could copy RNA into DNA came a few years later. The intensity of the research in both the process of reverse transcription and the enzyme RT was greatly stimulated by the recognition, in the mid-1980s, that human immunodeficiency virus (HIV) was a retrovirus and by the fact that the first successful anti-HIV drug, azidothymidine (AZT), is a substrate for RT. Although AZT monotherapy is a thing of the past, the most commonly prescribed, and most successful, combination therapies still involve one or both of the two major classes of anti-RT drugs. Although the basic mechanics of reverse transcription were worked out many years ago, and the first high-resolution structures of HIV RT are now more than 20 years old, we still have much to learn, particularly about the roles played by the host and viral factors that make the process of reverse transcription much more efficient in the cell than in the test tube. Moreover, we are only now beginning to understand how various host factors that are part of the innate immunity system interact with the process of reverse transcription to protect the host-cell genome, the host cell, and the whole host, from retroviral infection, and from unwanted retrotransposition.

Developing and Evaluating Inhibitors against the RNase H Active Site of HIV-1 Reverse Transcriptase

“…As described in the introduction, there are a few cases in which specific RNA primers must be generated and/or removed by the activity of RH. The cleavage at the 3= end of the RNA PPT is one of two RH cleavages that generate the RNA primer that is used to initiate second-strand viral DNA synthesis (8). As shown in Fig.…”

“…Lastly, RH cleaves near the junction of the tRNA Lys 3 primer (which serves as the primer for minus-strand DNA synthesis) and the viral DNA. This cleavage takes place 1 nucleotide from the RNA-DNA junction, leaving a riboA attached to the 3= end of the minus-strand DNA (8).…”

High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs

“…6j ). The malleability of dsDNA and DNA–RNA elongation substrates has been linked to RT processivity and fast polymerization rates 26 , 27 . By contrast, the nonprocessive and slow nature of initiation has been associated with the rigidity and width of A-form RNA helices 2 – 6 .…”

Transposable Elements: Classification, Identification, and Their Use As a Tool For Comparative Genomics

“…Both exogenous retroviruses and LTR retrotransposons contain a gag gene that encodes a viral particle coat and a pol gene that encodes a reverse transcriptase, ribonuclease H, and an integrase, which provide the enzymatic machinery for reverse transcription and integration into the host genome. Reverse transcription occurs within the viral or viral-like particle (GAG) in the cytoplasm, and it is a multistep process [34]. Unlike LTR retrotransposons, exogenous retroviruses contain an env gene, which encodes an envelope that facilitates their migration to other cells.…”