Manganese cations increase the mutation rate of human immunodeficiency virus type 1 ex vivo

Abstract : Human immunodeficiency virus (HIV) reverse transcription is an error-prone process with an overall mutation rate of ∼3·4×10 −5 per base per replication cycle. This rate can be modulated by changes in different components of the retrotranscription reaction. In particular, in vitro substitution of magnesium cations (Mg 2+ ) by manganese cations (Mn 2+ ) has been shown to increase misincorporation of deoxynucleotide triphosphates (dNTPs) and to alter substrate specificity. Here, it is shown that Mn 2+ also increases the HIV mutation rate ex vivo . Treatment of permissive cells with Mn 2+ and subsequent HIV infection resulted in at least 6-fold and 10-fold increases in the mutant and mutation frequencies respectively, thus illustrating a further example of how to influence HIV genetic variation.