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 approximately 3.4 x 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 (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.
Vartanian
Jean-Pierre
JP
Institut Pasteur, Unité de Rétrovirologie Moléculaire, 28 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Sala
Monica
M
Institut Pasteur, Unité de Rétrovirologie Moléculaire, 28 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Henry
Michel
M
Institut Pasteur, Unité de Rétrovirologie Moléculaire, 28 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Wain-Hobson
Simon
S
Institut Pasteur, Unité de Rétrovirologie Moléculaire, 28 rue du Dr Roux, 75724 Paris Cedex 15, France1.
Meyerhans
Andreas
A
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Klinikum Homburg, Haus 47, Universität des Saarlandes, 66421 Homburg/Saar, Germany2.
D002413:Cations, Divalent; D002712:Chlorides / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008345:Manganese / Q000494:pharmacology*; D017895:Manganese Compounds / Q000494:pharmacology; D016296:Mutagenesis; D014158:Transcription, Genetic / Q000187:drug effects; D020298:U937 Cells
D002413:Cations, Divalent; D002712:Chlorides; D017895:Manganese Compounds; D008345:Manganese; D054303:HIV Reverse Transcriptase; C025340:manganese chloride