HIV‐1 Proteases from Drug‐Naive West African Patients Are Differentially Less Susceptible to Protease Inhibitors

Kinomoto, Masanobu; Appiah–Opong, Regina; Brandful, James; Yokoyama, Masahiro; Nii-Trebi, Nicholas Israel; Ugly-Kwame, Evelyn; Sato, Hironori; Ofori‐Adjei, David; Kurata, Takeshi; Barré‐Sinoussi, Françoise; Sata, Tetsutaro; Tokunaga, Kenzo

doi:10.1086/431197

Cited by 60 publications

(42 citation statements)

References 35 publications

(42 reference statements)

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“…The alignments were generated using MOE-Align in the Molecular Operating Environment (MOE) package (Chemical Computing Group, Inc., Montreal, Quebec, Canada). 3-D models of SaV Mc10, FCV F4, and RHDV FRG 3C-like proteases were constructed by the homology modeling technique using MOE-Homology in the MOE package as described previously (17,18). The 3-D structures were thermodynamically optimized by energy minimization with the MOE package and an AMBER99 force field (31).…”

Section: Vol 81 2007 Sapovirus and Feline Calicivirus 3c-like Protementioning

confidence: 99%

Highly Conserved Configuration of Catalytic Amino Acid Residues among Calicivirus-Encoded Proteases

Oka

Yamamoto

Yokoyama

et al. 2007

J Virol

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, and H 137 in FCV. A computer-assisted structural analysis showed that despite high levels of diversity in the primary structures of the protease domains in the family Caliciviridae, the configurations of the H, E, C, and H residues are highly conserved, with these residues positioned closely along the inner surface of the potential binding cleft for the substrate. These results strongly suggest that the H, E, C, and H residues are involved in the formation of a conserved catalytic surface of the SaV and FCV 3C-like proteases.

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Section: Vol 81 2007 Sapovirus and Feline Calicivirus 3c-like Protementioning

confidence: 99%

Highly Conserved Configuration of Catalytic Amino Acid Residues among Calicivirus-Encoded Proteases

Oka

Yamamoto

Yokoyama

et al. 2007

J Virol

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“…[15][16][17] The impact of these genetic differences on the clinical response to antiretroviral therapy has yet to be fully assessed. [18][19][20][21][22][23][24] Nigeria is the most populous country in sub-Saharan Africa with a recent national census indicating a population exceeding 140 million. As in neighboring West African countries, HIV is thought to have entered the country in the mid-1980s.…”

Section: Introductionmentioning

confidence: 99%

Impact of HIV Type 1 Subtype on Drug Resistance Mutations in Nigerian Patients Failing First-Line Therapy

Chaplin

Eisen

Idoko

et al. 2011

AIDS Research and Human Retroviruses

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A diverse array of non-subtype B HIV-1 viruses circulates in Africa and dominates the global pandemic. It is important to understand how drug resistance mutations in non-B subtypes may develop differently from the patterns described in subtype B. HIV-1 reverse transcriptase and protease sequences from 338 patients with treatment failure to first-line ART regimens were evaluated. Multivariate logistic regression was used to examine the effect of subtype on each mutation controlling for regimen, time on therapy, and total mutations. The distribution of HIV-1 subtypes included CRF02_AG (45.0%), G (37.9%), CRF06_cpx (4.4%), A (3.6%), and other subtypes or recombinant sequences (9.2%). The most common NRTI mutations were M184V (89.1%) and thymidine analog mutations (TAMs). The most common NNRTI mutations were Y181C (49.7%), K103N (36.4%), G190A (26.3%), and A98G (19.5%). Multivariate analysis showed that CRF02_AG was less likely to have the M41L mutation compared to other subtypes [adjusted odds ratio (AOR) ¼ 0.35; p ¼ 0.022]. Subtype A patients showed a 42.5-fold increased risk (AOR ¼ 42.5, p ¼ 0.001) for the L210W mutation. Among NNRTI mutations, subtype G patients had an increased risk for A98G (AOR ¼ 2.40, p ¼ 0.036) and V106I (AOR ¼ 6.15, p ¼ 0.010), whereas subtype CRF02_AG patients had an increased risk for V90I (AOR ¼ 3.16; p ¼ 0.003) and a decreased risk for A98G (AOR ¼ 0.48, p ¼ 0.019). Five RT mutations were found to vary significantly between different non-B West African subtypes. Further study to understand the clinical impact of subtype-specific diversity on drug resistance will be critically important to the continued success of ART scale-up in resource-limited settings.

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“…HIV-1 non-B variants present clade-specific substitutions in positions related to drug resistance (26,52). They could accelerate the emergence of drug-resistant viruses, change or induce alternative pathways of resistance (17,19), influence viral replicative capacity in vitro (25), impair the interpretation of genotypic resistance algorithms (9,43,52), reduce the genetic barrier of certain protease inhibitors (47), and affect drug-binding affinity (27). Additionally, patients infected by certain HIV-1 non-B subtypes present accelerated disease pro-gression (2, 48) and higher cognitive impairment (40).…”

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Most HIV Type 1 Non-B Infections in the Spanish Cohort of Antiretroviral Treatment-Naïve HIV-Infected Patients (CoRIS) Are Due to Recombinant Viruses

et al. 2012

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HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02_AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected.

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HIV‐1 Proteases from Drug‐Naive West African Patients Are Differentially Less Susceptible to Protease Inhibitors

Abstract: These findings provide implications for the combination of PIs during the introduction of HAART into West Africa.

Cited by 60 publications

References 35 publications

Highly Conserved Configuration of Catalytic Amino Acid Residues among Calicivirus-Encoded Proteases

Highly Conserved Configuration of Catalytic Amino Acid Residues among Calicivirus-Encoded Proteases

Impact of HIV Type 1 Subtype on Drug Resistance Mutations in Nigerian Patients Failing First-Line Therapy

Most HIV Type 1 Non-B Infections in the Spanish Cohort of Antiretroviral Treatment-Naïve HIV-Infected Patients (CoRIS) Are Due to Recombinant Viruses

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