Use of Flaviviral genetic fragments as a potential prevention strategy for HIV-1 Silencing

  • Muhammad Sheraz Claflin University, Orangeburg, United States
  • Mazhar Kanak Claflin University, Orangeburg, United States
  • Mahmudul Hasan Claflin University, Orangeburg, United States
  • Roshan Bhattarai Claflin University, Orangeburg, United States
  • Kuhanandha Mahalingam Claflin University, Orangeburg, United States
  • Leanna A Sealey Claflin University, Orangeburg, United States
  • Rashshana R Blackwood Claflin University, Orangeburg, United States
  • Zhabiz Golkar Claflin University, Orangeburg, United States
  • Ewen McLean Claflin University, Orangeburg, United States
  • Omar Bagasra Claflin University, Orangeburg, United States
Keywords: Flaviviruses, HIV-1, miRNAs, vaccine

Abstract

Introduction: Coinfection with certain members of the Flaviviridae, such as Dengue Virus (DV), West Nile Virus (WNV) Yellow Fever Virus (YFV) and most importantly, GBV-C have been documented to reduce HIV-1 viral load in vivo. Numerous studies strongly support the notion that persistent coinfection with non-pathogenic virus prolongs survival in HIV-1 infected individuals. Coinfected individuals show higher CD4+ cell counts, lower HIV-1 RNA viral loads and live three times longer than clinically matched HIV-1 monoinfected patients. We have previously shown that one of the major anti-HIV defenses conferred by GBV-C coinfection is the upregulation of intracellular miRNAs in CD4+ cells that share significant mutual homologies with GBV-C and HIV-1 (>80%) genomes.

Methodology: Genome-wide bioinformatics analyses were carried out to search for miRNA binding sites in mutual homologies between HIV and several members of the Flaviviridae

Results:  Several miRNAs shared significant mutual homology with HIV-1 genetic sequences and GBV-A, B, C, DV, WNV and YFV.  These may be responsible for beneficial effects in HIV-1 infected individuals. Three highly mutual homologous miRNAs (i.e. miR-627-5, miR-369-5 and miR-548f), expressed in CD4+ cell lines, reduce HIV-1 replication by up to 90% whereas miRNAs with low mutual homologies (i.e. miR-34-1 and miR-508) impart only slight inhibition of HIV-1.

Conclusion: We hypothesize that a recombinant GBV-C-based vector can be constructed which expresses several beneficial genetic motifs of the Flaviviridae without causing any side effects while stimulating a wide array of beneficial miRNAs that can more efficiently prevent HIV-1 infection.

Author Biographies

Muhammad Sheraz, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Mazhar Kanak, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Mahmudul Hasan, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Roshan Bhattarai, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Kuhanandha Mahalingam, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Leanna A Sealey, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Rashshana R Blackwood, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Zhabiz Golkar, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Ewen McLean, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Omar Bagasra, Claflin University, Orangeburg, United States
South Carolina Center for Biotechnology, Claflin University, SC 29115, Orangeburg, United States
Published
2016-08-31
How to Cite
1.
Sheraz M, Kanak M, Hasan M, Bhattarai R, Mahalingam K, Sealey LA, Blackwood RR, Golkar Z, McLean E, Bagasra O (2016) Use of Flaviviral genetic fragments as a potential prevention strategy for HIV-1 Silencing. J Infect Dev Ctries 10:870-879. doi: 10.3855/jidc.7386
Section
Original Articles