Sequence variation of the human immunodeficiency virus primer-binding site suggests the use of an alternative tRNA(Lys) molecule in reverse transcription.

Retroviruses use a cellular tRNA molecule as primer for reverse transcription. The complementarity between the 3' end of this tRNA and a sequence near the 5' end of the viral RNA, the primer-binding site (PBS), allows the primer to anneal onto the viral RNA. During reverse transcription 18 nucleotides of the tRNA primer are copied into the viral cDNA, thereby regenerating the PBS sequence of the progeny. Thus, the PBS sequence reveals which primer was used. Human immunodeficiency viruses are known to replicate efficiently with tRNA(Lys3) as primer. Examination of the PBS sequence in natural and laboratory isolates indicates that a variant tRNA(Lys) is occasionally used as primer. This variant, for which the murine genomic sequence was described previously, was termed tRNA(Lys5) and differs from tRNA(Lys3) at five nucleotide positions. These results suggest that HIV uses both tRNA(Lys3) and tRNA(Lys5) molecules as primer, causing a switch of the PBS sequence.