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Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
- Source :
- Frontiers in Microbiology, Frontiers in Microbiology, Vol 12 (2021)
- Publication Year :
- 2021
-
Abstract
- HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms remain insufficiently validated. To clarify this issue, we recruited 52 treatment-naïve, HIV-1-infected patients in Tanzania, where multiple HIV-1 non-B subtypes co-circulate. Sequence analysis of 93 infectious envelope clones isolated from their plasma viral RNA revealed the co-circulation of subtypes A1, C, D, and inter-subtype recombinant forms (isRFs). Phenotypic tropism assays revealed that lentivirus reporters pseudotyped with 75 (80.6%) and 5 (5.4%) envelope clones could establish infection toward U87.CD4 cells expressing CCR5 (R5) and CXCR4 (X4), respectively; whereas the remaining 13 (14%) clones could infect both cells. Genotypic analyses by widely used algorithms including V3 net charge, Geno2pheno, WebPSSM, and PhenoSeq showed that almost all phenotypic X4-tropic clones and only 15 of 75 phenotypic R5-tropic clones were concordantly predicted. However, the remaining 60 phenotypic R5-tropic clones were discordantly predicted by at least one algorithm. In particular, 2 phenotypic R5-tropic clones were discordantly predicted by all algorithms tested. Taken together, the results demonstrate the limitation of currently available genotypic algorithms for predicting co-receptor inference among co-circulating multiple non-B subtypes and emerging isRFs. Also, the phenotypic tropism dataset presented here could be valuable for retraining of the widely used genotypic prediction algorithms to enhance their performance.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Co-receptor
Sequence analysis
viruses
030106 microbiology
envelope
non-B subtypes
Biology
Microbiology
law.invention
03 medical and health sciences
law
Genotype
medicine
Tropism
inter-subtype recombinant form
Original Research
Genetics
co-receptor tropism
virus diseases
biology.organism_classification
Phenotype
QR1-502
Entry inhibitor
030104 developmental biology
Lentivirus
Recombinant DNA
HIV-1
entry
medicine.drug
Subjects
Details
- ISSN :
- 1664302X
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in microbiology
- Accession number :
- edsair.doi.dedup.....01b6fa1317d4b75ad05ed9de41cc614c