The importance of glutamine 294 that affects the ribonuclease H activity of the reverse transcriptase of HIV-2 to viral replication
| Autor: | Eytan Herzig, Amnon Hizi |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
RNase H
RNase P Glutamine Ribonuclease H Mutant Reversions Mutation Missense Human immunodeficiency virus (HIV) Virus Replication medicine.disease_cause Virus Virology Reverse transcriptase Q294P HIV-2 RT mutation medicine Humans biology virus diseases RNA-Directed DNA Polymerase Reverse Transcription Molecular biology Amino Acid Substitution Viral replication HIV-2 HIV-1 biology.protein Mutant Proteins |
| Zdroj: | Virology. 483:13-20 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2015.04.018 |
| Popis: | Most currently-used antiretroviral drugs inhibit the reverse-transcriptase (RT) of HIV. The differences between HIV-1 and HIV-2 RTs explain why some of the anti-HIV-1 drugs are not effective against HIV-2. One major difference between the two HIV RTs is the low ribonuclease H (RNase H) activity of HIV-2 RT relative to HIV-1 RT. Our previous studies showed that residue Gln294 in HIV-2 RT accounts for this RNase H reduction (the comparable residue in HIV-1 RT is Pro294), as the Q294P mutant of HIV-2 RT has ~10-fold higher RNase H. Here, we show that infectious HIV-2 cannot bear the replacement of the RT׳s Gln294 by the HIV-1 RT Pro counterpart, as it results in substantially reduced HIV-2 replication and fast reversions to the wild-type Gln294 virus. These findings prove the critical role of maintaining low RT-associated RNase H activity in HIV-2. In contrast, HIV-1 can tolerate an about 10-fold higher RNase H. |
| Databáze: | OpenAIRE |
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