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

Human immunodeficiency virus (HIV) reverse transcription is an error-prone process with an overall mutation rate of similar to 3.4 x 10(-5) per base p er replication cycle. This rate can be modulated by changes in different co mponents of the retro-transcription reaction. In particular, in vitro subst itution of magnesium cations (Mg2+) by manganese cations (Mn2+) has been sh own to increase misincorporation of deoxynucleotide triphosphates (dNTPs) a nd to alter substrate specificity. Here, it is shown that Mn2+ also increas es the HIV mutation rate ex vivo. Treatment of permissive cells with Mn2+ a nd subsequent HIV infection resulted in at least 6-fold and 10-fold increas es in the mutant and mutation frequencies respectively, thus illustrating a further example of how to influence HIV genetic variation.