Sensitivity/Resistance Profile of a Simian Immunodeficiency Virus Containing the Reverse Transcriptase Gene of Human Immunodeficiency Virus Type 1 (HIV-1) Toward the HIV-1-Specific Non-nucleoside Reverse Transcriptase Inhibitors

Balzarini, Jan; Weeger, M; Camarasa, Marı́a-José; Declercq, E.; Überla, Klaus

doi:10.1006/bbrc.1995.1890

Cited by 44 publications

(31 citation statements)

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“…1A). The severe delay in RT/SHIV replication following transfection contrasts with the rapid replication following infection of cultured cells reported previously (6,7,22,31).…”

contrasting

confidence: 71%

“…To help alleviate these limitations, an RT/SHIV genome was constructed in which SIV RT sequences were replaced with HIV RT sequences (6). The kinetics of RT/ SHIV replication following recombinant DNA transfection was not included in the original or subsequent publications describing this recombinant (6,7,22,31). However, it was demonstrated that stocks of RT/SHIV replicated comparably to wild-type SIV in experimentally infected rhesus macaques (31) and that replication of RT/SHIV was significantly decreased by the administration of either class of RT inhibitor (6,7).…”

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confidence: 99%

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A Nucleotide Substitution in the tRNA ^Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Soderberg¹,

Denekamp

Nikiforow

et al. 2002

J Virol

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A recombinant simian immunodeficiency virus (SIV) derived from strain 239 (SIVmac239) with reverse transcriptase (RT) sequences from human immunodeficiency virus type 1 (HIV-1) strain HXB2 was severely impaired for replication. Detectable p27Gag levels were not observed until day 65 and peak p27 Gag levels were not reached until day 75 after transfection of CEMx174 cells with the recombinant DNA. Sequences from the latter time point did not contain amino acid substitutions in HIV-1 RT; however, a single nucleotide substitution (thymine to cytosine) was found at position eight of the SIV primer binding site. We engineered an RT/SHIV genome with the thymine-to-cytosine substitution, called RT/SHIV/TC, and observed dramatically faster replication kinetics than were observed with the parental RT/SHIV from which this variant was derived. RT/SHIV/TC provides an improved system for study of the impact of drug resistance mutations in HIV-1 RT in a relevant animal model.

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“…1A). The severe delay in RT/SHIV replication following transfection contrasts with the rapid replication following infection of cultured cells reported previously (6,7,22,31).…”

contrasting

confidence: 71%

mentioning

confidence: 99%

A Nucleotide Substitution in the tRNA ^Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Soderberg¹,

Denekamp

Nikiforow

et al. 2002

J Virol

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“…This limitation has been circumvented by construction of chimeric viruses (RT-SHIVs), which consist of SIV molecular clones in which the SIV RT has been replaced with the HIV-1 RT (2, 63). Two different RTSHIVs have been used for studies of AIDS therapy in rhesus macaques (6,30,43) and pigtail macaques (3). The first RT-SHIV, which is the one we used in this study, was made from the pathogenic molecular clone SIVmac239 (63).…”

mentioning

confidence: 99%

“…The first RT-SHIV, which is the one we used in this study, was made from the pathogenic molecular clone SIVmac239 (63). This RT-SHIV is susceptible to NRTIs and several NNRTIs, including nevirapine and efavirenz (6,30). Moreover, RT-SHIV mutants resistant to NNRTIs selected in vitro arise as rapidly as with HIV-1 and contain similar mutations (6,30).…”

mentioning

confidence: 99%

Viral Sanctuaries during Highly Active Antiretroviral Therapy in a Nonhuman Primate Model for AIDS

North¹,

Higgins²,

Deere³

et al. 2010

J Virol

155

171

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“…A more successful strategy has been to replace the entire SIV mac239 RT with HIV-1 HXB2 RT (RT-SHIV mac239 ) (5,46). RT-SHIV mac239 is as sensitive to NNRTIs as HIV-1.…”

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confidence: 99%

In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques

Ambrose

Boltz

Palmer

et al. 2004

J Virol

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Antiviral resistance is a significant obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Because nonnucleoside reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus (SIV) RT, the development of animal models to study the evolution of antiviral resistance has been problematic. To facilitate in vivo studies of NNRTI resistance, we examined whether a SIV that causes immunopathogenesis in pigtail macaques could be made sensitive to NNRTIs. Two simian-human immunodeficiency viruses (SHIVs) were derived from the genetic background of SIV mne : SIV-RT-YY contains RT substitutions intended to confer NNRTI susceptibility (V181Y and L188Y), and RT-SHIV mne contains the entire HIV-1 RT coding region. Both mutant viruses grew to high titers in vitro but had reduced fitness relative to wild-type SIV mne . Although the HIV-1 RT was properly processed into p66 and p51 subunits in RT-SHIV mne particles, the RT-SHIV mne virions had lower levels of RT per viral genomic RNA than HIV-1. Correspondingly, there was decreased RT activity in RT-SHIV mne and SIV-RT-YY particles. HIV-1 and RT-SHIV mne were similarly susceptible to the NNRTIs efavirenz, nevirapine, and UC781. However, SIV-RT-YY was less sensitive to NNRTIs than HIV-1 or RT-SHIV mne . Classical NNRTI resistance mutations were selected in RT-SHIV mne after in vitro drug treatment and were monitored in a sensitive allelespecific real-time RT-PCR assay. Collectively, these results indicate that RT-SHIV mne may be a useful model in macaques for the preclinical evaluation of NNRTIs and for studies of the development of drug resistance in vivo.

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Sensitivity/Resistance Profile of a Simian Immunodeficiency Virus Containing the Reverse Transcriptase Gene of Human Immunodeficiency Virus Type 1 (HIV-1) Toward the HIV-1-Specific Non-nucleoside Reverse Transcriptase Inhibitors

Cited by 44 publications

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A Nucleotide Substitution in the tRNA ^Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

A Nucleotide Substitution in the tRNA ^Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Viral Sanctuaries during Highly Active Antiretroviral Therapy in a Nonhuman Primate Model for AIDS

In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques

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Sensitivity/Resistance Profile of a Simian Immunodeficiency Virus Containing the Reverse Transcriptase Gene of Human Immunodeficiency Virus Type 1 (HIV-1) Toward the HIV-1-Specific Non-nucleoside Reverse Transcriptase Inhibitors

Cited by 44 publications

References 0 publications

A Nucleotide Substitution in the tRNA Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

A Nucleotide Substitution in the tRNA Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Viral Sanctuaries during Highly Active Antiretroviral Therapy in a Nonhuman Primate Model for AIDS

In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques

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A Nucleotide Substitution in the tRNA ^Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase

A Nucleotide Substitution in the tRNA ^Lys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase