Статья

Consensus integrase of a new HIV-1 genetic variant CRF63_02A1

Y. Agapkina, M. Pustovarova, S. Korolev, D. Zyryanova, V. Ivlev, A. Totmenin, N. Gashnikova, M. Gottikh,
2021

The high genetic variability of the human immunodeficiency virus (HIV-1) leads to a constant emergence of new genetic variants, including the recombinant virus CRF63_02A1, which is widespread in the Siberian Federal District of Russia. We studied HIV-1 CRF63_02A1 integrase (IN_CRF) catalyzing the incorporation of viral DNA into the genome of an infected cell. The consensus sequence was designed, recombinant integrase was obtained, and its DNA-binding and catalytic activities were characterized. The stability of the IN_CRF complex with the DNA substrate did not differ from the complex stability for subtype A and B integrases; however, the rate of complex formation was significantly higher. The rates and efficiencies of 3'-processing and strand transfer reactions catalyzed by IN_CRF were found to be higher, too. Apparently, all these distinctive features of IN_CRF may result from specific amino acid substitutions in its N-terminal domain, which plays an important role in enzyme multimerization and binding to the DNA substrate. It was also found that the drug resistance mutations Q148K/G140S and G118R/E138K significantly reduce the catalytic activity of IN_CRF and its sensitivity to the strand transfer inhibitor raltegravir. Reduction in sensitivity to raltegravir was found to be much stronger in the case of double-mutation Q148K/G140S. © 2019 National Research University Higher School of Economics.

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • Y. Agapkina
    Lomonosov Moscow State University, Chemistry Department and Belozersky Institute of Physical Chemical Biology, Leninskie gory 1/40, Moscow, 119991, Russian Federation
  • M. Pustovarova
    State Research Center of Virology and Biotechnology 'Vector', Koltsovo, 630559, Russian Federation
  • S. Korolev
  • D. Zyryanova
  • V. Ivlev
  • A. Totmenin
  • N. Gashnikova
  • M. Gottikh
Название журнала
  • Acta Naturae
Том
  • 11
Выпуск
  • 1
Страницы
  • 14-22
Издатель
  • Acta Naturae
Тип документа
  • journal article
Источник
  • scopus