scholarly journals Coreceptor Usage, Diversity, and Divergence in Drug-Naive and Drug-Exposed Individuals from Malawi, Infected with HIV-1 Subtype C for More Than 20 Years

2014 ◽  
Vol 30 (10) ◽  
pp. 975-983 ◽  
Author(s):  
Ishla Seager ◽  
Simon A. Travers ◽  
Michael D. Leeson ◽  
Amelia C. Crampin ◽  
Neil French ◽  
...  
Keyword(s):  
Coreceptor Usage ◽  
Subtype C ◽  
Drug Naïve ◽  
Hiv 1

scholarly journals Functional and genetic analysis of coreceptor usage by dualtropic HIV-1 subtype C isolates

Virology ◽  
2009 ◽  
Vol 393 (1) ◽  
pp. 56-67 ◽  
Author(s):  
Ashika Singh ◽  
Taryn Page ◽  
Penny L. Moore ◽  
Rachel L. Allgaier ◽  
Keshni Hiramen ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Coreceptor Usage ◽  
Subtype C ◽  
Hiv 1

scholarly journals Characterization of V3 Sequence Heterogeneity in Subtype C Human Immunodeficiency Virus Type 1 Isolates from Malawi: Underrepresentation of X4 Variants

1999 ◽  
Vol 73 (8) ◽  
pp. 6271-6281 ◽  
Author(s):  
Li-Hua Ping ◽  
Julie A. E. Nelson ◽  
Irving F. Hoffman ◽  
Jody Schock ◽  
Suzanna L. Lamers ◽  
...  
Keyword(s):  
Basic Amino Acid ◽  
Coreceptor Usage ◽  
Sequence Variability ◽  
Subtype C ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Pcr Products ◽  
V3 Region ◽  
Hiv 1

ABSTRACT We have examined the nature of V3 sequence variability among subtype C human immunodeficiency virus type 1 (HIV-1) sequences from plasma-derived viral RNA present in infected men from Malawi. Sequence variability was assessed by direct sequence analysis of the V3 reverse transcription-PCR products, examination of virus populations by a subtype C V3-specific heteroduplex tracking assay (V3-HTA), and selected sequence analysis of molecular clones derived from the PCR products. Sequence variability in V3 among the subtype C viruses was not associated with the presence of basic amino acid substitutions. This observation is in contrast to that for subtype B HIV-1, where sequence variability is associated with such substitutions, and these substitutions are determinants of altered coreceptor usage. Evolutionary variants in subtype C V3 sequences, as defined by the V3-HTA, were not correlated with the CD4 level in the infected person, while such a correlation was found with subtype B V3 sequences. Viruses were isolated from a subset of the subjects; all isolates used CCR5 and not CXCR4 as a coreceptor, and none was able to grow in MT-2 cells, a hallmark of the syncytium-inducing phenotype that is correlated with CXCR4 usage. The overall sequence variability of the subtype C V3 region was no greater than that of the conserved regions of gp120. This limited sequence variability was also a feature of subtype B V3 sequences that do not carry the basic amino acid substitutions associated with altered coreceptor usage. Our results indicate that altered coreceptor usage is rare in subtype C HIV-1 isolates in sub-Saharan Africa and that sequence variability is not a feature of the V3 region of env in the absence of altered coreceptor usage.

HIV-1 subtype C syncytium- and non-syncytium-inducing phenotypes and coreceptor usage among Ethiopian patients with AIDS

AIDS ◽  
1999 ◽  
Vol 13 (11) ◽  
pp. 1305-1311 ◽  
Author(s):  
Almaz Abebe ◽  
Dereje Demissie ◽  
Jaap Goudsmit ◽  
Margreet Brouwer ◽  
Carla L. Kuiken ◽  
...  
Keyword(s):  
Coreceptor Usage ◽  
Subtype C ◽  
Hiv 1

scholarly journals Prediction of coreceptor usage by five bioinformatics tools in a large Ethiopian HIV-1 subtype C cohort

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0182384 ◽  
Author(s):  
Amare Worku Kalu ◽  
Nigus Fikrie Telele ◽  
Solomon Gebreselasie ◽  
Daniel Fekade ◽  
Samir Abdurahman ◽  
...  
Keyword(s):  
Coreceptor Usage ◽  
Subtype C ◽  
Bioinformatics Tools ◽  
Hiv 1

scholarly journals Potential Associations of Mutations within the HIV-1 Env and Gag Genes Conferring Protease Inhibitor (PI) Drug Resistance

2021 ◽  
Vol 12 (4) ◽  
pp. 967-977
Author(s):  
Ntombikhona F. Maphumulo ◽  
Michelle L. Gordon
Keyword(s):  
Protease Inhibitor ◽  
Viral Fitness ◽  
Site Directed Mutagenesis ◽  
Envelope Gene ◽  
Subtype C ◽  
Exact Test ◽  
Number Of Patients ◽  
Drug Naïve ◽  
The Impact ◽  
Hiv 1

An increasing number of patients in Africa are experiencing virological failure on a second-line antiretroviral protease inhibitor (PI)-containing regimen, even without resistance-associated mutations in the protease region, suggesting a potential role of other genes in PI resistance. Here, we investigated the prevalence of mutations associated with Lopinavir/Ritonavir (LPV/r) failure in the Envelope gene and the possible coevolution with mutations within the Gag-protease (gag-PR) region. Env and Gag-PR sequences generated from 24 HIV-1 subtype C infected patients failing an LPV/r inclusive treatment regimen and 344 subtype C drug-naïve isolates downloaded from the Los Alamos Database were analyzed. Fisher’s exact test was used to determine the differences in mutation frequency. Bayesian network probability was applied to determine the relationship between mutations occurring within the env and gag-PR regions and LPV/r treatment. Thirty-five mutations in the env region had significantly higher frequencies in LPV/r-treated patients. A combination of Env and Gag-PR mutations was associated with a potential pathway to LPV/r resistance. While Env mutations were not directly associated with LPV/r resistance, they may exert pressure through the Gag and minor PR mutation pathways. Further investigations using site-directed mutagenesis are needed to determine the impact of Env mutations alone and in combination with Gag-PR mutations on viral fitness and LPV/r efficacy.

HIV-1 Subtype C Reverse Transcriptase Sequences from Drug-Naive Pregnant Women in South Africa

2002 ◽  
Vol 18 (8) ◽  
pp. 605-610 ◽  
Author(s):  
Candice Pillay ◽  
Helba Bredell ◽  
James McIntyre ◽  
Glenda Gray ◽  
Lynn Morris
Keyword(s):  
South Africa ◽  
Reverse Transcriptase ◽  
Pregnant Women ◽  
Subtype C ◽  
Drug Naïve ◽  
Hiv 1

scholarly journals CoRSeqV3-C: a novel HIV-1 subtype C specific V3 sequence based coreceptor usage prediction algorithm

Retrovirology ◽  
2013 ◽  
Vol 10 (1) ◽  
pp. 24 ◽  
Author(s):  
Kieran Cashin ◽  
Lachlan R Gray ◽  
Martin R Jakobsen ◽  
Jasminka Sterjovski ◽  
Melissa J Churchill ◽  
...  
Keyword(s):  
Prediction Algorithm ◽  
Coreceptor Usage ◽  
Subtype C ◽  
Hiv 1

Emergence of HIV-1 C/A1 and C/A1/D circulating recombinant forms, and dominance of subtype C and R5 use from whole genome sequence analysis in Addis Ababa

2019 ◽  
Author(s):  
Melaku Adal ◽  
Kate El Bouzidi ◽  
Adane Mihret ◽  
Rawleigh Howe ◽  
Abraham Aseffa ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Addis Ababa ◽  
Cd4 T Cell ◽  
Whole Genome ◽  
Coreceptor Usage ◽  
Subtype C ◽  
Cell Counts ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract Background The HIV pandemic in Ethiopia is dominated by subtype C with sporadic A and D epidemiology. The presence of subtypes A and D may result in emergence of recombinant viruses, and increase the genetic diversity that makes monitoring the HIV epidemic, and the development of vaccines and therapeutics difficult. This study is aimed at determining subtypes, circulating recombinant forms (CRFs), and the dominant coreceptor use in Addis Ababa, Ethiopia. Methods Participants with a range of purposely selected CD4+ T-cell counts were included. Chi-square and Mann-Whitney tests were used. Whole genome next-generation sequencing (NGS) of HIV was performed using a PCR amplification method and Illumina MiSeq. Subtyping and scanning of recombination were done by the REGA subtyping tool version 3.0. Prediction of coreceptor usage was performed using Geno2Pheno clonal-model and PhenoSeq. Signature amino acids and positive charges were also used in the tropism prediction. Phylogenetic analyses were conducted with MEGA version 6 using maximum likelihood with the neighbor-joining (N-J) methods. Results Sixty participants were included with a median age of 34.5 [interquartile range (IQR) 30.0-40.0]. Seven (11.7%) of the study participants were at WHO clinical stage 3/4 and 13 (21.7%) were at AIDS stage with CD4+ T cell count <200 cells/uL. Among the total 60 HIV genomes sequenced, 49 were subtype C (81.7%), one was subtype A1 (1.7%), six were recombinant C/A1 (10%), three were recombinant C/A1/D (5.0%), and one was unassigned. From 50 of the sequences where coreceptor usage was determined by PhenoSeq, 44 (88.0%) were CCR5-tropic and six (12.0%) used CXCR4. Conclusion The study confirmed that the dominant subtype in Addis Ababa is HIV-1 subtype C. In addition, HIV-1 subtype A1, CRFs C/A1 and C/A1/D were also identified. The dominance of R5-tropic viruses was detected and these were associated with a higher CD4 T-cell count and lower viral load. Further studies on HIV subtypes and CRFs will be essential to fully understand HIV/AIDS epidemiology. In addition, the tropism information is important in Ethiopia if the use of the co-receptor antagonist maraviroc is planned.

scholarly journals A Reliable Phenotype Predictor for Human Immunodeficiency Virus Type 1 Subtype C Based on Envelope V3 Sequences

2006 ◽  
Vol 80 (10) ◽  
pp. 4698-4704 ◽  
Author(s):  
Mark A. Jensen ◽  
Mia Coetzer ◽  
Angélique B. van 't Wout ◽  
Lynn Morris ◽  
James I. Mullins
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Coreceptor Usage ◽  
Subtype C ◽  
Subtype B ◽  
Combining Data ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT In human immunodeficiency virus type 1 (HIV-1) subtype B infections, the emergence of viruses able to use CXCR4 as a coreceptor is well documented and associated with accelerated CD4 decline and disease progression. However, in HIV-1 subtype C infections, responsible for more than 50% of global infections, CXCR4 usage is less common, even in individuals with advanced disease. A reliable phenotype prediction method based on genetic sequence analysis could provide a rapid and less expensive approach to identify possible CXCR4 variants and thus increase our understanding of subtype C coreceptor usage. For subtype B V3 loop sequences, genotypic predictors have been developed based on position-specific scoring matrices (PSSM). In this study, we apply this methodology to a training set of 279 subtype C sequences of known phenotypes (228 non-syncytium-inducing [NSI] CCR5+ and 51 SI CXCR4+ sequences) to derive a C-PSSM predictor. Specificity and sensitivity distributions were estimated by combining data set bootstrapping with leave-one-out cross-validation, with random sampling of single sequences from individuals on each bootstrap iteration. The C-PSSM had an estimated specificity of 94% (confidence interval [CI], 92% to 96%) and a sensitivity of 75% (CI, 68% to 82%), which is significantly more sensitive than predictions based on other methods, including a commonly used method based on the presence of positively charged residues (sensitivity, 47.8%). A specificity of 83% and a sensitivity of 83% were achieved with a validation set of 24 SI and 47 NSI unique subtype C sequences. The C-PSSM performs as well on subtype C V3 loops as existing subtype B-specific methods do on subtype B V3 loops. We present bioinformatic evidence that particular sites may influence coreceptor usage differently, depending on the subtype.

scholarly journals HIV-1 Reverse Transcriptase Nucleotide Substitutions in Subtype C–Infected, Drug-Naive, and Treatment-Experienced Patients in South India

2011 ◽  
Vol 58 (3) ◽  
pp. e94-e95
Author(s):  
Shanmugam Saravanan ◽  
Vidya Madhavan ◽  
Pachamuthu Balakrishnan ◽  
Sunil S. Solomon ◽  
Nagalingeswaran Kumarasamy ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
South India ◽  
Subtype C ◽  
Nucleotide Substitutions ◽  
Drug Naïve ◽  
Hiv 1
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