AN INCREASE IN THE INFECTIVITY OF THE HUMAN IMMUNODEFICIENCY VIRUS WITH MODIFICATION OF THE CCR5 GENE RECEPTOR OF SENSITIVE CELLS

Abstract

Identification of a natural mutation of the ccr5 gene in humans which makes them resistant to HIV-1 infection, has opened a new direction for the development of alternative treatment approaches through genome editing. The human immunodeficiency virus, when infecting CD4+ cells, uses one of two chemokine co-receptors of the plasma membrane. During infection and in the early stages of infection, strains using the CCR5 protein circulate, while the later ones use the CXCR4 protein. It cannot be ruled out that there is a complex relationship in the regulation of the expression of these receptors, which in turn can affect the replication of the virus in cells that normally do not have the CCR5 protein on the membrane. To study the effect of ccr5 gene correction on HIV-1 replication in the in vitro system, exactly like this MT-4 cell line was used. The study of virus replication showed that genetic modification of the ccr5 gene of MT-4 cells led to an increase in the activity of the studied HIV-1 strains, and this increase was most pronounced in homozygous variant. Our results indicate that editing the genome of human cells should be treated with great caution and that such studies require in-depth and comprehensive study.