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

Institut Pasteur, Unité de Rétrovirologie Moléculaire, 28 rue du Dr Roux, 75724 Paris Cedex 15, France¹
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Klinikum Homburg, Haus 47, Universität des Saarlandes, 66421 Homburg/Saar, Germany²

Author for correspondence: Jean-Pierre Vartanian.Fax +33 1 45 68 88 74. e-mail jpvart{at}pasteur.fr

Human immunodeficiency virus (HIV) reverse transcription is an error-prone process with an overall mutation rate of ~3·4x10^-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 (Mg²⁺) by manganese cations (Mn²⁺) has been shown to increase misincorporation of deoxynucleotide triphosphates (dNTPs) and to alter substrate specificity. Here, it is shown that Mn²⁺ also increases the HIV mutation rate ex vivo. Treatment of permissive cells with Mn²⁺ 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.

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