Chemokine Coreceptor Usage Among HIV-1 Drug-Naive Patients Residing in the Rural Eastern Cape, South Africa
AIDS RESEARCH AND HUMAN RETROVIRUSES
Authors: Digban, Tennison Onoriode; Iweriebor, Benson Chucks; Nwodo, Uchechukwu U.; Okoh, Anthony Ifeanyi; Obi, Larry Chikwelu
Abstract
Sub-Saharan region in Africa still holds the highest burden of HIV/AIDS globally. HIV-1 requires coreceptor to gain entry into permissive cells to initiate infection. Molecular analysis of the chemokine coreceptor usage is important clinically and in the effective management of AIDS virus. This study aims to determine the coreceptor usage among HIV-1 drug-naive patients residing in the rural Eastern cape, South Africa. We collected blood samples from 55 HIV-infected patients into an anticoagulant vacutainer. RNA was extracted from separated plasma, and reverse transcription-polymerase chain reaction (RT-PCR) was performed followed by nested polymerase chain reaction to amplify the partial envelope fragment spanning the C2-C3 region. Sanger sequencing was done on the amplicons using the BigDye Terminator V3.1 sequencing kit (Applied Biosystems, Foster City, CA) while sequences were manually edited using BioEdit and Geneious 10.2.6 tools. The WebPSSM and Geno2pheno online tools were also utilized to predict coreceptor tropism while the phylogenetic analysis of the isolates was determined using MEGA 7. Of the 55 blood samples collected for the study, 50 (91%) were successfully amplified and sequenced. The mean age of the patients was 32 (18-56) years while the ratio of men to women was 35% and 65% correspondingly. Phylogenetic analysis revealed that all 50 sequences clustered with HIV-1 subtype C reference strains. Viral tropism of the V3 loop revealed 47 sequences to be R5 strains, while three sequences (T1E, T10E, and T11E,) were classified as X4 strains based on the WebPSSM and the Geno2pheno algorithm. HIV-1 R5 tropic strains were the most dominant virus obtained from this study, while HIV-1 subtype C still drives the epidemic in South Africa suggesting greaterin vivoand host pathogen fitness. Documented data on mapping out cellular tropism based on viral tropism are important as maraviroc and the other CCR5 antagonist could be introduced as part of the treatment regimen in South Africa.
MiRNA-1246 suppresses the proliferation and migration of renal cell carcinoma through targeting CXCR4
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
Authors: Liu, H-T; Fan, W-X
Abstract
OBJECTIVE: To uncover the role of miRNA-1246 in influencing the proliferative and migratory capacities of RCC by binding CX-CR4 and downregulating its level. PATIENTS AND METHODS: Relative levels of miRNA-1246 and CXCR4 in 40 paired RCC tissues and adjacent normal tissues were determined. The binding relationship between miRNA-1246 and CXCR4 was confirmed by Dual-Lu-ciferase reporter assay. Proliferative and migratory abilities of RCC regulated by miRNA-1246 and CXCR4 were assessed. RESULTS: MiRNA-1246 was downregulated in RCC tissues and cell lines. Overexpression of miRNA-1246 attenuated proliferative and migratory capacities of 786-O and 769-P cells. CXCR4 was the direct target of miRNA-1246 and its level was negatively regulated by miRNA-1246. Silence of CXCR4 inhibited RCC to proliferate and migrate. CONCLUSIONS: MiRNA-1246 attenuates proliferative and migratory abilities of RCC by downregulating CXCR4. MiRNA-1246/CXCR4 axis could be potential therapeutic target for RCC.