Identification of a clinical isolate of HIV-1 with an isoleucine at position 82 of the protease which retains susceptibility to protease inhibitors

King, R. H.; Winslow, Dean L.; Garber, Sena; Scarnati, Helen; Bachelor, Lee; Stack, Sylvia; Otto, Michael

doi:10.1016/0166-3542(95)00033-i

Cited by 21 publications

(16 citation statements)

References 28 publications

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“…In patient C7, a V82I substitution was present in all clones amplified during a blip to 148 copies/ml following recent nonadherence. This substitution, while not typically observed with nelfinavir failure, could represent a preexisting polymorphism or an uncommon early resistance mutation (23). At 3 months later, the viral load was Ͻ50 copies/ml and we were unable to detect persistent low-level viremia with our assay.…”

Section: Discussionmentioning

confidence: 70%

Continued Production of Drug-Sensitive Human Immunodeficiency Virus Type 1 in Children on Combination Antiretroviral Therapy Who Have Undetectable Viral Loads

Persaud¹,

Siberry²,

Ahonkhai

et al. 2004

J Virol

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Highly active antiretroviral therapy (HAART) can suppress plasma human immunodeficiency virus type 1 (HIV-1) levels to below the detection limit of ultrasensitive clinical assays. However, HIV-1 persists in cellular reservoirs, and in adults, persistent low-level viremia is detected with more sensitive assays. The nature of this viremia is poorly understood, and it is unclear whether viremia persists in children on HAART, particularly those who start therapy shortly after birth. We therefore developed a reverse transcriptase PCR (RT-PCR) assay that allows genotyping of HIV-1 protease even when viremia is present at levels as low as 5 copies of HIV-1 RNA/ml. We demonstrated that viremia persists in children with plasma virus levels below the limit of detection of clinical assays. Viremia was detected even in children who began HAART in early infancy and maintained such strong suppression of viremia that HIV-1-specific antibody responses were absent or minimal. The low-level plasma virus lacked protease inhibitor resistance mutations despite the frequent use of nelfinavir, which has a low mutational barrier to resistance. Protease sequences resembled those of viruses in the latent reservoir in resting CD4 ؉ T cells. Thus, in most children on HAART with clinically undetectable viremia, there is continued virus production without evolution of resistance in the protease gene.

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Section: Discussionmentioning

confidence: 70%

Continued Production of Drug-Sensitive Human Immunodeficiency Virus Type 1 in Children on Combination Antiretroviral Therapy Who Have Undetectable Viral Loads

Persaud¹,

Siberry²,

Ahonkhai

et al. 2004

J Virol

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“…Este estudo tem por objetivo comparar a genotipagem e subtipagem do HIV-1 em crianças experimentadas e virgens de tratamento e comparar os perfis de resistência aos medicamentos usados através da genotipagem nessas crianças. [24][25][26][27][28] .…”

Section: Introductionunclassified

Diversity and prevalence of antiretroviral genotypic resistance mutations among HIV-1-infected children

Almeida¹,

Berezin²,

Rodrigues³

et al. 2009

J Pediatr (Rio J)

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ResumoObjetivo: Avaliar a genotipagem e subtipagem em crianças experimentadas e virgens de tratamento, assim como perfis de resistência a medicamentos através da genotipagem nessas crianças. Conclusion:Our results show low rates of primary resistance in ARV-naïve children and high rates of resistance in children failing ARV treatment, which is compatible with ARV use in these patients.J Pediatr (Rio J). 2009;85(2):104-109: HIV, resistance, genotype, child, antiretroviral therapy. Artigo submetido em 08.09.08, aceito em 21.01.09.

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“…Although the HERV-K group comes closest of all known HERVs to containing infectious virus, no corresponding replication-competent virus has so far been described (1,3). Although humans harbor several dozen proviral copies of HERV type K per haploid genome (4,6,7), some of which code for the characteristic retroviral proteins Gag, Pol, and Env (8,9), recent studies raised a suggestion that no complete proviral copy of HERV-K exists (10,11); the issue remains to be clarified. In terms of infectious virion production, HERV-K could be defective at multiple levels, including the observed arrest during budding, inefficient RT enzyme activity, and incomplete Env expression and processing (1).…”

mentioning

confidence: 99%

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

Kuhelj¹,

Rizzo²,

Chang

et al. 2001

Journal of Biological Chemistry

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A full-length and C-terminally truncated version of human endogenous retrovirus (HERV)-K10 protease were expressed in Escherichia coli and purified to homogeneity. Both versions of the protease efficiently processed HERV-K10 Gag polyprotein substrate. HERV-K10 Gag was also cleaved by human immunodeficiency virus, type 1 (HIV-1) protease, although at different sites. To identify compounds that could inhibit protein processing dependent on the HERV-K10 protease, a series of cyclic ureas that had previously been shown to inhibit HIV-1 protease was tested. Several symmetric bisamides acted as very potent inhibitors of both the truncated and full-length form of HERV-K10 protease, in subnanomolar or nanomolar range, respectively. One of the cyclic ureas, SD146, can inhibit the processing of in vitro translated HERV-K10 Gag polyprotein substrate by HERV-K10 protease. In addition, in virus-like particles isolated from the teratocarcinoma cell line NCCIT, there is significant accumulation of Gag and Gag-Pol precursors upon treatment with SD146, suggesting the compound efficiently blocks HERV-K Gag processing in cells. This is the first report of an inhibitor able to block cell-associated processing of Gag polypeptides of an endogenous retrovirus.

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Identification of a clinical isolate of HIV-1 with an isoleucine at position 82 of the protease which retains susceptibility to protease inhibitors

Cited by 21 publications

References 28 publications

Continued Production of Drug-Sensitive Human Immunodeficiency Virus Type 1 in Children on Combination Antiretroviral Therapy Who Have Undetectable Viral Loads

Continued Production of Drug-Sensitive Human Immunodeficiency Virus Type 1 in Children on Combination Antiretroviral Therapy Who Have Undetectable Viral Loads

Diversity and prevalence of antiretroviral genotypic resistance mutations among HIV-1-infected children

Inhibition of Human Endogenous Retrovirus-K10 Protease in Cell-free and Cell-based Assays

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