G-->A hypermutation of the human immunodeficiency virus type 1 genome: evidence for dCTP pool imbalance during reverse transcription.

Jean Pierre Vartanian (1) , A. Meyerhans (1) , M. Sala (1) , S. Wain-Hobson (1)

1 Rétrovirologie Moléculaire

The quasispecies model for RNA viruses predicts the existence of a replication error threshold beyond which there is a melting or total loss of sequence information. Retroviral G-->A hypermutation is probably an example. Here it is shown that G-->A transitions may occur in both GpG and GpA dinucleotide contexts. Transitions in GpG preferentially occur via base mispairing at the ends of runs of G residues, whereas G-->A transitions within GpA may result from temporary dislocation of the primer and template strands by a single base. The two circumstances may be related by the local dCTP substrate concentration. An in vitro elongation assay shows that primer/template dislocation is more frequent for the human immunodeficiency virus type 1 reverse transcriptase than for murine or avian retroviral enzymes. Taken together these data suggest that G-->A hypermutation is an example of induced mutation whereby the viral reverse transcriptase is forced into making errors by imbalances in the intracellular dCTP concentration.

Domains: Life Sciences [q-bio]

Jean Pierre Vartanian, A. Meyerhans, M. Sala, S. Wain-Hobson. G-->A hypermutation of the human immunodeficiency virus type 1 genome: evidence for dCTP pool imbalance during reverse transcription.. Proceedings of the National Academy of Sciences of the United States of America, 1994, 91 (8), pp.3092-3096. ⟨10.1073/pnas.91.8.3092⟩. ⟨pasteur-03520165⟩