Efficient pre-catalytic conformational change of reverse transcriptases from SAMHD1 non-counteracting primate lentiviruses during dNTP incorporation.
Virology
; 537: 36-44, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31442614
ABSTRACT
Unlike HIV-1, HIV-2 and some SIV strains replicate at high dNTP concentrations even in macrophages due to their accessory proteins, Vpx or Vpr, that target SAMHD1 dNTPase for proteasomal degradation. We previously reported that HIV-1 reverse transcriptase (RT) efficiently synthesizes DNA even at low dNTP concentrations because HIV-1 RT displays faster pre-steady state kpol values than SAMHD1 counteracting lentiviral RTs. Here, since the kpol step consists of two sequential sub-steps post dNTP binding, conformational change and chemistry, we investigated which of the two sub-steps RTs from SAMHD1 non-counteracting viruses accelerate in order to complete reverse transcription in the limited dNTP pools found in macrophages. Our study demonstrates that RTs of SAMHD1 non-counteracting lentiviruses have a faster conformational change rate during dNTP incorporation, supporting that these lentiviruses may have evolved to harbor RTs that can efficiently execute the conformational change step in order to circumvent SAMHD1 restriction and dNTP depletion in macrophages.
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Base de dados:
MEDLINE
Assunto principal:
DNA Polimerase Dirigida por RNA
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Lentivirus de Primatas
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Desoxirribonucleotídeos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article