The Molecules of HIV

Note: this site last updated in 2006

reverse transcriptase

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

The enzyme reverse transcriptase (RT) is unique to retroviruses such as HIV - human cells don't normally need to carry out any reverse transcription.

HIV-1 RT is composed of two molecular subunits - called p66 and p51 (since their weight is 66 kD and 51 kD). In fact, p51 is effectively just a "truncated" form of p66, although the two proteins do actually fold up differently after production.

RT is the number-one target for drug therapy. Most HAART therapies contain a RT-inhibitor component.

Well-known RT-inhibitors include zidovudine (aka AZT) and tenofovir. These act as nucleoside analogues - in a sense they "pretend" to be a nucleoside so that when RT is creating new DNA it "accidentally" inserts a molecule of zidovudine (or tenofovir) rather than a nucleoside. This terminates the DNA chain and no more can be appended to it. Other nucleoside analogues which inhibit RT are ddI, ddC, and d4T.

There are also many non-nucleoside reverse transcriptase inhibitors (NNRTIs) which don't work by pretending to be a nucleoside. Often they simply try to "jam" reverse transcriptase more directly, by becoming bound to the RT enzyme.

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Written by
Dan Stowell

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