Open AccessUse of Flaviviral genetic fragments as a potential prevention strategy for HIV-1 Silencing
Author(s) -
Muhammad Sheraz,
Mazhar A. Kanak,
Mahmudul Hasan,
Roshan Bhattarai,
Kuhanandha Mahalingam,
Leanna Sealey,
Rashshana R Blackwood,
Zhabiz Golkar,
Ewen McLean,
Omar Bagasra
Publication year - 2016
Publication title -
journal of infection in developing countries
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.322
H-Index - 49
eISSN - 2036-6590
pISSN - 1972-2680
DOI - 10.3855/jidc.7386
Subject(s) - coinfection , biology , virology , flaviviridae , gb virus c , virus , dengue fever , viral load , dengue virus , gene silencing , flavivirus , viral replication , microrna , genetics , hepatitis c virus , gene
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.