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

Mbondji-Wonje, Christelle

Dong, Ming

Zhao, Jiangqin

Wang, Xue

Nanfack, Aubin

Ragupathy, Viswanath

Sanchez, Ana M

Denny, Thomas N

Hewlett, Indira

2020-09-08T17:53:49Z

2020-09-08T17:53:49Z

2020-08-06

2020-09-08T17:53:45Z

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.

10.1038/s41598-020-70083-1

2045-2322

2045-2322

https://hdl.handle.net/10161/21415

eng

Springer Science and Business Media LLC

Scientific reports

10.1038/s41598-020-70083-1

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

Journal article

13214

1

School of Medicine

Duke Human Vaccine Institute

Duke Global Health Institute

Medicine, Duke Human Vaccine Institute

Duke

Institutes and Centers

University Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Clinical Science Departments

Published

10