Gene-editing technology identifies new HIV treatment targets
New York: Using a gene-editing technology, scientists have identified three human genes essential for HIV infection, a finding that may promise new targets for treatment of the deadly infection.
HIV virus has only nine genes, while humans have more than 19,000. Thus, viruses take control of human genes to make essential building blocks for their replication, the study said.
The study focussed on human immune cells T cells, the primary targets of HIV, and to identify host genes with the most dramatic role in viral infection of T cells.
“Our goal was to identify human genes, also called host genes, that are essential for HIV to replicate but could be eliminated without harming a human patient,” said Bruce Walker, Professor at Harvard Medical School in Boston, US.
In the study, using CRISPR to screen a cell line derived from HIV-susceptible CD4 T cells, the scientists identified five genes that, when inactivated, protected cells from HIV infection without affecting cellular survival.
In addition to CD4 and CCR5, the screen identified genes for two enzymes — TPST2 and SLC35B2 — that modify the CCR5 molecule in a way that is required for the binding of HIV.
An additional gene identified through the screen was ALCAM, which is involved in cell-to-cell adhesion. When CD4 T cells are exposed to low amounts of virus, as might be seen in natural transmission, loss of ALCAM was associated with striking protection from HIV infection.
The study demonstrates how CRISPR-based screens can be applied to identify host factors critical to the survival of other viral pathogens but dispensable for host cell viability.
“CRISPR makes it possible to completely knock out genes at the DNA level; and our genome-wide, CRISPR-Cas9-based approach targets more than 18,500 genes, the vast majority of human protein-coding genes,” explained Tim Wang, doctoral student at Whitehead Institute for Biomedical Research — a non-profit research institution in Massachusetts, US.
The study was published in the journal Nature Genetics.