Browsing by Author "Zhao, Jiangqin"

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    Distinctive variation in the U3R region of the 5' Long Terminal Repeat from diverse HIV-1 strains.
    (PloS one, 2018-01) Mbondji-Wonje, Christelle; Dong, Ming; Wang, Xue; Zhao, Jiangqin; Ragupathy, Viswanath; Sanchez, Ana M; Denny, Thomas N; Hewlett, Indira
    Functional mapping of the 5'LTR has shown that the U3 and the R regions (U3R) contain a cluster of regulatory elements involved in the control of HIV-1 transcription and expression. As the HIV-1 genome is characterized by extensive variability, here we aimed to describe mutations in the U3R from various HIV-1 clades and CRFs in order to highlight strain specific differences that may impact the biological properties of diverse HIV-1 strains. To achieve our purpose, the U3R sequence of plasma derived virus belonging to different clades (A1, B, C, D, F2) and recombinants (CRF02_AG, CRF01_AE and CRF22_01A1) was obtained using Illumina technology. Overall, the R region was very well conserved among and across different strains, while in the U3 region the average inter-strains nucleotide dissimilarity was up to 25%. The TAR hairpin displayed a strain-distinctive cluster of mutations affecting the bulge and the loop, but mostly the stem. Like in previous studies we found a TATAA motif in U3 promoter region from the majority of HIV-1 strains and a TAAAA motif in CRF01_AE; but also in LTRs from CRF22_01A1 isolates. Although LTRs from CRF22_01A1 specimens were assigned CRF01_AE, they contained two NF-kB sites instead of the single TFBS described in CRF01_AE. Also, as previously describe in clade C isolates, we found no C/EBP binding site directly upstream of the enhancer region in CRF22_01A1 specimens. In our study, one-third of CRF02_AG LTRs displayed three NF-kB sites which have been mainly described in clade C isolates. Overall, the number, location and binding patterns of potential regulatory elements found along the U3R might be specific to some HIV-1 strains such as clade F2, CRF02_AG, CRF01_AE and CRF22_01A1. These features may be worth consideration as they may be involved in distinctive regulation of HIV-1 transcription and replication by different and diverse infecting strains.
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    Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms.
    (Scientific reports, 2020-08-06) Mbondji-Wonje, Christelle; Dong, Ming; Zhao, Jiangqin; Wang, Xue; Nanfack, Aubin; Ragupathy, Viswanath; Sanchez, Ana M; Denny, Thomas N; Hewlett, Indira
    The critical role of the regulatory elements at the 5' end of the HIV-1 genome in controlling the life cycle of HIV-1 indicates that this region significantly influences virus fitness and its biological properties. In this study, we performed a detailed characterization of strain-specific variability of sequences from the U5 to upstream of the gag gene start codon of diverse HIV-1 strains by using next-generation sequencing (NGS) techniques. Overall, we found that this region of the HIV-1 genome displayed a low degree of intra-strain variability. On the other hand, inter-strain variability was found to be as high as that reported for gag and env genes (13-17%). We observed strain-specific single point and clustered mutations in the U5, PBS, and gag leader sequences (GLS), generating potential strain-specific transcription factor binding sites (TFBS). Using an infrared gel shift assay, we demonstrated the presence of potential TFBS such as E-box in CRF22_01A, and Stat 6 in subtypes A and G, as well as in their related CRFs. The strain-specific variation found in the sequence corresponding at the RNA level to functional domains of the 5' UTR, could also potentially impact the secondary/tertiary structural rearrangement of this region. Thus, the variability observed in this 5' end of the genomic region of divergent HIV-1 strains strongly suggests that functions of this region might be affected in a strain-specific manner. Our findings provide new insights into DNA-protein interactions that regulate HIV-1 replication and the influence of strain characterization on the biology of HIV-1 infection.