Skip to main content

Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms.

Publication ,  Journal Article
Mbondji-Wonje, C; Dong, M; Zhao, J; Wang, X; Nanfack, A; Ragupathy, V; Sanchez, AM; Denny, TN; Hewlett, I
Published in: Sci Rep
August 6, 2020

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 6, 2020

Volume

10

Issue

1

Start / End Page

13214

Location

England

Related Subject Headings

  • gag Gene Products, Human Immunodeficiency Virus
  • Transcription Factors
  • Species Specificity
  • Recombination, Genetic
  • RNA, Viral
  • High-Throughput Nucleotide Sequencing
  • HIV-1
  • Genetic Variation
  • Binding Sites
  • 5' Untranslated Regions
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Mbondji-Wonje, C., Dong, M., Zhao, J., Wang, X., Nanfack, A., Ragupathy, V., … Hewlett, I. (2020). Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms. Sci Rep, 10(1), 13214. https://doi.org/10.1038/s41598-020-70083-1
Mbondji-Wonje, Christelle, Ming Dong, Jiangqin Zhao, Xue Wang, Aubin Nanfack, Viswanath Ragupathy, Ana M. Sanchez, Thomas N. Denny, and Indira Hewlett. “Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms.Sci Rep 10, no. 1 (August 6, 2020): 13214. https://doi.org/10.1038/s41598-020-70083-1.
Mbondji-Wonje C, Dong M, Zhao J, Wang X, Nanfack A, Ragupathy V, et al. Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms. Sci Rep. 2020 Aug 6;10(1):13214.
Mbondji-Wonje, Christelle, et al. “Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms.Sci Rep, vol. 10, no. 1, Aug. 2020, p. 13214. Pubmed, doi:10.1038/s41598-020-70083-1.
Mbondji-Wonje C, Dong M, Zhao J, Wang X, Nanfack A, Ragupathy V, Sanchez AM, Denny TN, Hewlett I. Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms. Sci Rep. 2020 Aug 6;10(1):13214.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 6, 2020

Volume

10

Issue

1

Start / End Page

13214

Location

England

Related Subject Headings

  • gag Gene Products, Human Immunodeficiency Virus
  • Transcription Factors
  • Species Specificity
  • Recombination, Genetic
  • RNA, Viral
  • High-Throughput Nucleotide Sequencing
  • HIV-1
  • Genetic Variation
  • Binding Sites
  • 5' Untranslated Regions