Shutting down specific genes triggers apoptosis in HIV-infected macrophages and may be a viable curative approach for those infected with HIV, according to the results of a genome-wide screening study published in BMC Infectious Diseases.
Human monocyte cell lines (U937 and THP-1) were used to facilitate pooled genome-wide screening of new gene targets based on short-haired RNA that induce apoptosis of macrophages that are infected with HIV-enhanced green fluorescent protein (eGFP ) or infected by HIV heat are stable antigen (HSA). Small interfering RNAs from target proteins were transfected into the cells and apoptosis was determined by flow cytometry.
The researchers observed that 28 genes were consistently linked to the survival of HIV-infected cells.
After transfection, apoptosis was induced (P <0.1) in cells infected with HIV-eGFP and HIV-HAS, with 12 and 6 genes being switched off, respectively.
The researchers identified a final set of 4 of the top candidate genes that significantly increased apoptosis induction (P <.05): the cytochrome c oxidase gene 7A2, COX7A2; the zinc finger protein 484 gene, ZNF484; the cyclin-dependent kinase 2 gene, CDK2; and the cleavage stimulating factor subunit 2 tau variant gene, CSTF2T.
Compared to uninfected cells, the knockdown of COX7A2, ZNF484, CDK2, or CSTF2T resulted in up to 60% of infected macrophages and 15% of uninfected macrophages undergoing apoptosis. Additionally, the researchers reported that some uninfected cells did not survive the transfection process, suggesting that some of the cell death was likely due to transfection rather than gene silencing.
The researchers investigated whether gene silencing induces apoptosis in HIV-exposed cells. Compared to uninfected cells, HIV bystander cells transfected with COX7A2, CDK2 or CSTf2T showed a significantly increased induction of apoptosis (15% vs. 10%), albeit to a lesser extent than infected cells (50% vs. 10%) ).
The researchers observed that switching off COX7A2 disrupted respiratory chain complexes II and IV and increased the production of reactive oxygen species.
This study was limited as it remains unclear whether these results can be translated into effective clinical interventions for people with HIV infection.
These data indicate the potential of gene-targeting silencing to induce apoptosis, particularly in HIV-infected cells.
Dong SXM, Vizeacoumar FS, Bhanumathy KK et al. Identification of new genes involved in apoptosis of HIV-infected macrophages through unbiased, genome-wide screening. BMC Infect Dis. 2021; 21 (1): 655. doi: 10.1186 / s12879-021-06346-7
This article originally appeared on Infectious Disease Advisor