IMAT 2018 Q29 [Reverse Transcriptase]

Reverse transcriptase is mainly found in retroviruses such as HIV. Four nucleotides are needed for the reaction catalysed by this enzyme.

A group of molecules may inhibit this enzyme. These molecules are structurally similar to the nucleotides but slightly altered so that bonds normally formed in the reaction cannot be made.

Which of the following statements may be correct?

  1. The four inhibitor molecules will resemble adenine, thymine, guanine and cytosine.
  2. The inhibitor molecules can prevent the formation of phosphodiester bonds.
  3. The inhibitor molecules can result in a reduction in the number of new virus particles
    produced.

A. 1 and 3 only
B. 1, 2 and 3
C. 3 only
D. 1 and 2 only
E. 2 and 3 only

This is a practical question where we need to apply our knowledge. Let’s start with a recall of reverse transcriptase: it is an enzyme that catalyzes the conversion of RNA back into DNA (hence why it is named after reverse transcription). We also need to recall the difference between DNA nucleotides (adenine, thymine, guanine and cytosine), and RNA nucleotides (adenine, uracil, guanine and cytosine). Finally, we need to consider the different processes involved in forming RNA and DNA molecules because an inhibitor could work by preventing any of these steps. Without going into too much detail, we know that we need to add nucleotides and join them with phosphodiester bonds between them in order to form a strand of polynucleotides.

Now that we have a bit of background, let’s break down the statements:

1. The four inhibitor molecules will resemble adenine, thymine, guanine and cytosine.

Since we are going from RNA to DNA, we need adenine, thymine, guanine, and cytosine. We do not need uracil because we want to make DNA only, not more RNA. Therefore the inhibitors could resemble adenine, thymine, guanine, and cytosine if you wanted to prevent the addition of these nucleotides to the growing strand. Therefore 1 is correct.

2. The inhibitor molecules can prevent the formation of phosphodiester bonds.

If the inhibitors prevented the formation of phosphodiester bonds, then the addition of nucleotides to the sequence would not be allowed, which is needed in any form of polynucleotide (DNA, RNA, etc) synthesis. Therefore 2 must be correct.

3. The inhibitor molecules can result in a reduction in the number of new virus particles produced.

If you are inhibiting reverse transcriptase, it is not allowing the genetic information to be integrated with the host’s DNA cell (viral RNA needs to be converted into DNA in order to be integrated into the host). This would prevent viral DNA from being replicated and would also prevent viral proteins and RNA from assembling to form new particles, therefore it would reduce the number of new virus particles produced. 3 is correct.

\fcolorbox{red}{grey!30}{Therefore the answer must be B as all are correct.}