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Maintaining the reading frame during translation is central to the accuracy and fidelity of translation. However, many retroviruses, including HIV, the human immunodeficiency virus that causes AIDS, take advantage of mRNA slippage and a change in reading frame to generate different proteins from the same message.

A single mRNA, the gag-pol messenger, encodes two polyproteins that overlap by about 200 nucleotides and are in different reading frames. The gag polyprotein is translated from the initiation codon to an in-frames termination codon near the gag-pol junction; gag polyprotein is then cleaved to generate several structural proteins of the virus. However, about 5% of the time a one-nucleotide frameshift occurs within the overlapping segment of mRNA and the termination codon is bypassed because it is no longer in the reading frame. Instead a gag-pol fusion polyprotein is produced. Proteolytic cleavage of the pol polyprotein produces the viral reverse transcripitase and other proteins needed in virus reproduction.