title: The importance of glutamine 294 that affects the ribonuclease H activity of the reverse transcriptase of HIV-2 to viral replication.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69974, Israel.
authors.forename: Eytan
authors.initials: E
authors.lastname: Herzig
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69974, Israel. Electronic address: ahizy@post.tau.ac.il.
authors.forename: Amnon
authors.initials: A
authors.lastname: Hizi
mesh_terms: D019943:Amino Acid Substitution; D005973:Glutamine / Q000235:genetics / Q000378:metabolism*; D015498:HIV-2 / Q000201:enzymology* / Q000502:physiology*; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D048348:Reverse Transcription; D016914:Ribonuclease H / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D050505:Mutant Proteins; D005973:Glutamine; D012194:RNA-Directed DNA Polymerase; D016914:Ribonuclease H
keywords: HIV-1; HIV-2; Q294P HIV-2 RT mutation; RNase H; Reverse transcriptase; Reverse transcription; Reversions; Virus replication