Ninety-Nine Is Not Enough: Molecular Characterization of Inhibitor-Resistant Human Immunodeficiency Virus Type 1 Protease Mutants with Insertions in the Flap Region

Kožíšek, Milan; Šašková, Klára Grantz; Řezáčová, P.; Brynda, J.; Maarseveen, Noortje M van; Jong, Dorien de; Boucher, Charles A.; Kagan, Ron M.; Nijhuis, Monique; Konvalinka, Jan

doi:10.1128/jvi.02325-07

Cited by 38 publications

(47 citation statements)

References 47 publications

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“…In the presence of the ins35TN and resistance mutations, the replication level was lower than when the resistance mutations were present with ins35G 8 . On the other hand, studies have shown that ins33L and ins35E can favor resistance to protease inhibitors 9 . The virus circulating in our patient did not exhibit a high resistance level to any protease inhibitor, but showed intermediate resistance to nelfinavir and potentially low-level resistance to atazanavir/r, fosamprenavir/r, indinavir/r and lopinavir/r.…”

Section: Introductionmentioning

confidence: 99%

“…These variants could show an advantage in proliferation in the presence of drug selection pressure 5,8,9 .…”

Section: Introductionmentioning

confidence: 99%

“…Insertions in codon 35 of PR have recently been reported [7][8][9] , but their impact on enzymatic activity, viral biology and resistance to protease inhibitors (PI) remains unknown 8 . These variants could show an advantage in proliferation in the presence of drug selection pressure 5,8,9 .…”

Section: Introductionmentioning

confidence: 99%

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A first case of protease codon 35 amino acid insertion in a HIV-1 subtype B sequence detected in the Bauru region, state of São Paulo, Brazil: case report

Grotto

Corvino

Munhoz

et al. 2011

Rev. Soc. Bras. Med. Trop.

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Amino acid insertions in the protease have rarely been described in HIVinfected patients. One of these insertions has recently been described in codon 35, although its impact on resistance remains unknown. This study presents a case of an HIV variant with an insertion in codon 35 of the protease, described for the first time in Bauru, State of Sao Paulo, Brazil, circulating in a 38-year-old caucasian male with asymptomatic HIV infection since 1997. The variant isolated showed a codon 35 insertion of two amino acids in the protease: a threonine and an aspartic acid, resulting in the amino acid sequence E35E_TD.

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Section: Introductionmentioning

confidence: 99%

“…These variants could show an advantage in proliferation in the presence of drug selection pressure 5,8,9 .…”

Section: Introductionmentioning

confidence: 99%

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A first case of protease codon 35 amino acid insertion in a HIV-1 subtype B sequence detected in the Bauru region, state of São Paulo, Brazil: case report

Grotto

Corvino

Munhoz

et al. 2011

Rev. Soc. Bras. Med. Trop.

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“…1 A heterogeneous group of insertion mutations ranging from 3 to 18 nucleotides has been identified in HIV-1 strains at positions 17,19,22,25,31,33,35,36,37,70, and 95 of the protease (PR) coding region. [2][3][4][5][6][7][8] These insertion mutations are likely generated by the RT stalling and primer/template slippage that is also believed to generate RT insertion mutations. 9,10 Amino acid insertions in the PR coding region have been reported * Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

Detection of the protease codon 35 amino acid insertion in sequences from treatment-naïve HIV-1 subtype C infected individuals in the Central Region of Portugal

Pereira‐Vaz

Duque

Trindade³

et al. 2009

Journal of Clinical Virology

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Results: A threonine insertion (E35E T) was detected in 2.69% (n = 7) of the sequences analyzed and all the sequences that possessed this insertion were identified as subtype C. All the seven inserted sequences clustered in the same lineage of the phylogenetic tree. Heterosexual and intravenous drug use were found to be the routes of infection. No major mutations in the PR coding region associated with resistance to PIs were detected. Conclusions: It was found the highest prevalence of PR codon 35 insertion among treatment-naïve HIV-1 infected individuals ever reported in the western countries. Epidemiological data and Phylogenetic analysis indicated the possibility of transmission of this insertion. The results suggested that these inserted strains have normal susceptibility to PIs containing regimens. This study demonstrated the spreading epidemic of PR codon 35 inserted strains from subtype C in the Central Region of Portugal, during the past eight years.

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“…combination of PI with other antiretrovirals, mainly inhibitors of the HIV reverse transcriptase, increased the life expectancy of of HIV-positive patients . 3,4 The mechanism of HIV protease, it's drug-resistant and their interactions with different inhibitors have been studied for nearly 20 years to combat the challenges of AIDS & drug resistance. 5 HIV protease plays a crucial role in viral maturation, multiplication and producing infectious virus particles.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Rumex Vesicarius Linn and Symplocos Racemosa Roxb as Probable Hiv-Protease Inhibitors

Manure¹,

Naikwade²

2017

Int. Res. J. Pharm.

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The objective of the present study to evaluate in-vitro antiviral activity of different extracts of leaves of Rumex vesicarius Linn and Symplocos racemosa Roxb. In this study in-vitro antiviral activity was assayed by pepsin. Pepsin was used as a substitute for HIV-protease to evaluate inhibitory activity of these plants, as pepsin has close resemblance with HIV-protease in proteolytic activity. We have evaluated antiviral activity of different extracts of leaves of Rumex vesicarius Linn and Symplocos racemosa Roxb. But neither different extract of leaves of Rumex vesicarius Linn shows antiviral activity or protease inhibitory activity nor different extract of leaves of Symplocos racemosa Roxb. We have used pepstatin A as a standard (Positive control) which is a natural inhibitor of pepsin enzyme. The study demonstrated that the different extracts of Rumex vesicarius Linn and Symplocos racemosa Roxb did not show antiviral activity or protease inhibitory activity.

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Ninety-Nine Is Not Enough: Molecular Characterization of Inhibitor-Resistant Human Immunodeficiency Virus Type 1 Protease Mutants with Insertions in the Flap Region

Cited by 38 publications

References 47 publications

A first case of protease codon 35 amino acid insertion in a HIV-1 subtype B sequence detected in the Bauru region, state of São Paulo, Brazil: case report

A first case of protease codon 35 amino acid insertion in a HIV-1 subtype B sequence detected in the Bauru region, state of São Paulo, Brazil: case report

Detection of the protease codon 35 amino acid insertion in sequences from treatment-naïve HIV-1 subtype C infected individuals in the Central Region of Portugal

Evaluation of Rumex Vesicarius Linn and Symplocos Racemosa Roxb as Probable Hiv-Protease Inhibitors

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