V3 Net Charge: Additional Tool in HIV-1 Tropism Prediction

2014 ◽  
Vol 30 (12) ◽  
pp. 1203-1212 ◽  
Author(s):  
Claudia Montagna ◽  
Elisa De Crignis ◽  
Isabella Bon ◽  
Maria Carla Re ◽  
Ivano Mezzaroma ◽  
...  
Keyword(s):  
Net Charge ◽  
Additional Tool ◽  
Hiv 1 ◽  
Tropism Prediction

scholarly journals X4 Tropic Virus Prediction Is Associated with a Nadir CD4 T-Cell Count below 100 Cells/mm3

Intervirology ◽  
2015 ◽  
Vol 58 (3) ◽  
pp. 155-159 ◽  
Author(s):  
Matthieu Sechet ◽  
Catherine Roussel ◽  
Jean-Luc Schmit ◽  
Carlo Saroufim ◽  
Kamel Ghomari ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
False Positive Rate ◽  
Cd4 T Cell ◽  
Ccr5 Antagonist ◽  
Net Charge ◽  
Antagonist Therapy ◽  
Hiv 1 ◽  
Cd4 T Cell Count ◽  
Tropism Prediction

Objective: The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients. Methods: Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed. Results: According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01). Conclusion: We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm3 that must be taken into account when considering a CCR5 antagonist therapy switch.

Short Communication: Severe Immune Suppression in Patients Infected with R5-Tropic HIV-1 Strains Is Associated with Increased gp120 Net Charge at Variable Regions

2011 ◽  
Vol 27 (9) ◽  
pp. 965-967 ◽  
Author(s):  
Eduardo Seclén ◽  
Vincent Soriano ◽  
María del Mar González ◽  
Juan González-Lahoz ◽  
Eva Poveda
Keyword(s):  
Immune Suppression ◽  
Short Communication ◽  
Net Charge ◽  
Variable Regions ◽  
Hiv 1

scholarly journals Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier

2013 ◽  
Vol 68 (7) ◽  
pp. 1471-1485 ◽  
Author(s):  
Francisco Díez-Fuertes ◽  
Elena Delgado ◽  
Yolanda Vega ◽  
Aurora Fernández-García ◽  
María Teresa Cuevas ◽  
...  
Keyword(s):  
Bayesian Network ◽  
Coreceptor Tropism ◽  
Bayesian Network Classifier ◽  
Hiv 1 ◽  
Tropism Prediction

Coreceptor Tropism and Maraviroc Sensitivity of Clonally Derived Ethiopian HIV-1C Strains Using an in-house Phenotypic Assay and Commonly Used Genotypic Methods

2018 ◽  
Vol 16 (2) ◽  
pp. 113-120
Author(s):  
Amare Worku Kalu ◽  
Nigus Fikrie Telele ◽  
Shambhu G Aralaguppe ◽  
Solomon Gebre-Selassie ◽  
Daniel Fekade ◽  
...  
Keyword(s):  
Dose Response ◽  
In Vitro Activity ◽  
Coreceptor Tropism ◽  
Phenotypic Assay ◽  
Subtype B ◽  
Hiv 1 ◽  
Tropism Prediction ◽  
Alternative Regimen

Objectives:Genotypic Tropism Testing (GTT) tools are generally developed based on HIV-1 subtype B (HIV-1B) and used for HIV-1C as well but with a large discordance of prediction between different methods. We used an established phenotypic assay for comparison with GTT methods and for the determination of in vitro maraviroc sensitivity of pure R5-tropic and dual-tropic HIV-1C.Methods:Plasma was obtained from 58 HIV-1C infected Ethiopians. Envgp120 was cloned into a luciferase tagged NL4-3 plasmid. Phenotypic tropism was determined by in house method and the V3 sequences were analysed by five GTT methods. In vitro maraviroc sensitivity of R5-tropic and dual-tropic isolates were compared in the TZMbl cell-line.Results:The phenotypes were classified as R5 in 92.4% and dual tropic (R5X4) in 7.6% of 79 clones. The concordance between phenotype and genotype ranged from 64.7% to 84.3% depending on the GTT method. Only 46.9% of the R5 phenotypes were predicted as R5 by all GTT tools while R5X4 phenotypes were predicted as X4 by four methods, but not by Raymond’s method. All six tested phenotypic R5 clones, as well as five of six of dual tropic clones, showed a dose response to maraviroc.Conclusion:There is a high discordance between GTT methods, which underestimates the presence of R5 and overestimates X4 strains compared to a phenotypic assay. Currently available GTT algorithms should be further improved for tropism prediction in HIV-1C. Maraviroc has an in vitro activity against most HIV-1C viruses and could be considered as an alternative regimen in individuals infected with CCR5-tropic HIV-1C viruses.

scholarly journals Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net charge

Virology ◽  
2008 ◽  
Vol 379 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Johanna Repits ◽  
Jasminka Sterjovski ◽  
Daniel Badia-Martinez ◽  
Mattias Mild ◽  
Lachlan Gray ◽  
...  
Keyword(s):  
Viral Fitness ◽  
Net Charge ◽  
Stage Disease ◽  
End Stage ◽  
Hiv 1

scholarly journals Appraisal of a Simple and Effective RT-qPCR Assay for Evaluating the Reverse Transcriptase Activity in Blood Samples from HIV-1 Patients

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1047
Author(s):  
Beatrice Macchi ◽  
Caterina Frezza ◽  
Francesca Marino-Merlo ◽  
Antonella Minutolo ◽  
Valeria Stefanizzi ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Quantitative Pcr ◽  
Replication Capacity ◽  
Functional Screening ◽  
Pcr Assay ◽  
Blood Samples ◽  
Additional Tool ◽  
Wide Range ◽  
Hiv 1 ◽  
Quantitative Pcr Assay

Testing HIV-1 RNA in plasma by PCR is universally accepted as the ultimate standard to confirm diagnosis of HIV-1 infection and to monitor viral load in patients under treatment. However, in some cases, this assay could either underestimate or overestimate the replication capacity of a circulating or latent virus. In the present study, we performed the assessment of evaluating the HIV-1 reverse transcriptase (RT) activity by means of a new assay for the functional screening of the status of HIV-1 patients. To this purpose, we utilized, for the first time on blood samples, an adapted version of a real-time RT quantitative PCR assay, utilized to evaluate the HIV-1-RT inhibitory activity of compounds. The study analyzed blood samples from 28 HIV-1-infected patients, exhibiting a wide range of viremia and immunological values. Results demonstrated that plasma HIV-1 RT levels, expressed as cycle threshold values obtained with the assay under appraisal, were inversely and highly significantly correlated with the plasma HIV-1-RNA levels of the patients. Thus, an HIV-1 RT quantitative PCR assay was created which we describe in this study, and it may be considered as a promising basis for an additional tool capable of furnishing information on the functional virological status of HIV-1-infected patients.

scholarly journals Evaluation of genotypic tropism prediction tests compared with in vitro co-receptor usage in HIV-1 primary isolates of diverse subtypes

2011 ◽  
Vol 67 (1) ◽  
pp. 25-31 ◽  
Author(s):  
E. Delgado ◽  
A. Fernandez-Garcia ◽  
Y. Vega ◽  
T. Cuevas ◽  
M. Pinilla ◽  
...  
Keyword(s):  
Receptor Usage ◽  
Hiv 1 ◽  
Tropism Prediction

scholarly journals Mechanisms and evolutionary implications of integration of different functions within HIV-1 Tat

2021 ◽  
Author(s):  
Margarita A. Kurnaeva ◽  
Arthur O. Zalevsky ◽  
Eugene A. Arifulin ◽  
Olga M. Lisitsyna ◽  
Anna V. Tvorogova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Viral Proteins ◽  
Net Charge ◽  
Origin And Evolution ◽  
Nuclear Localization Signals ◽  
Protein Size ◽  
Charged Amino Acids ◽  
A Charge ◽  
Hiv 1 ◽  
Positively Charged

During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses.

scholarly journals Improving HIV-1 tropism determination by combining geno2pheno and V3 net charge calculation

2012 ◽  
Vol 15 (6(Suppl 4)) ◽  
Author(s):  
M Montagna ◽  
E De Crignis ◽  
O Turriziani ◽  
I Bon ◽  
M Re ◽  
...  
Keyword(s):  
Net Charge ◽  
Hiv 1
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