The Molecules of HIV

Note: this site last updated in 2006

reverse transcription

An article from "The Molecules of HIV" (c) Dan Stowell

Transcription is the process of copying a DNA code into RNA. Commonly, in cells, a (DNA) gene which encodes a particular protein will be copied into "messenger RNA" (mRNA for short), and then the mRNA is transported to the section of the cell where proteins are made. (A good analogy for this is that the DNA genome is a library. In order to make yourself a protein you need to go to library, find the right book [gene], and take a photocopy [mRNA molecule] of the instructions so that you can take them away and use them.)

Reverse transcription, then, is the opposite process: copying RNA into DNA. Once the HIV particle has fused with a cell, an enzyme which it has brought with it - called reverse transcriptase - can copy HIV's RNA genome into DNA, ready to be integrated into the cell's DNA genome. This DNA version of the HIV genome has a Long Terminal Repeat at each end, which helps with the integration process. Another of HIV's proteins, RNase H, helps by degrading the RNA part of RNA-DNA hybrid molecules that form as part of this process.

Reverse transcriptase, by the way, is not an awfully good copier. It has been estimated that during each round of HIV-1 replication, 10 mistakes (such as incorrect coding "letters" or missed-out bits of code) are incorporated. This is a lot worse than, for example, an ordinary cell's transcription process, which has mechanisms in place to reduce the number of errors made. In fact this poor fidelity in the transcription is part of the reason HIV is so difficult to defend against - it means that the pattern of HIV genes and proteins changes quite rapidly, too rapidly for the immune system to keep up with.

The next step is integration into the host genome. (Although we describe reverse transcription as a separate stage from integration, these two processes do actually overlap. The RNA, reverse transcriptase, integrase, and other HIV proteins form a "pre-integration complex" which moves into the cell's nucleus. The reverse transcription begins, and integration begins at roughly the same time - HIV DNA is being integrated as quickly as it is being produced.)

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Written by
Dan Stowell

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