New advances in CRISPR gene editing could lead to a cure for HIV

0

The Human Immunodeficiency Virus (HIV) virus is a small, nondescript virus with only 12 proteins and a genome only a third the size of SARS-CoV-2. Nonetheless, it manages to hijack the body’s cells to replicate and spread across systems with impressive speed and agility. how does it do that

Northwestern Medicine scientists are using new advances in CRISPR gene-editing technology to unravel this mystery and hopefully lead to a new permanent treatment for the virus, according to a statement released by the institution on Friday. Through this process, they uncovered 86 genes that may play a role in the way HIV replicates, including over 40 that had never before been studied in the context of HIV infection.

Important tools in the fight against HIV

“Existing drug treatments are one of our most important tools in the fight against the HIV epidemic and have been amazingly effective in suppressing viral replication and spread,” said Judd Hultquist of Northwestern, one of the corresponding authors. “But these treatments are not curative, so people living with HIV must follow a strict treatment regimen that requires continued access to good, affordable health care – this is just not the world we live in.”

Hultquist’s study looked at T cells. These powerful cells targeted by HIV were isolated from human donor blood and hundreds of their genes were further knocked out using CRISPR-Cas9 gene editing. They were then infected with HIV to be examined. The researchers found that the loss of a gene important for viral replication in these cells led to reduced HIV infection, while the loss of an antiviral factor led to increased HIV infection.

Treatments that become remedies

“This is really great evidence that the steps and processes we took to conduct the study were robust and well thought out,” said Hultquist. “The fact that almost half of the genes we found were previously discovered increases the confidence in our data set. The exciting part is that more than half – 46 – of these genes have never been previously studied in the context of HIV infection, so they represent new potential therapeutic avenues to explore.”

Hultquist now hopes their work will lead to the development of new treatments that may become permanent cures. The study was published in the journal nature communication.

Abstract:

Human immunodeficiency virus (HIV) relies on the host’s molecular machinery for replication. Systematic attempts to define these host factors genetically or biochemically have generated hundreds of candidates, but only a few have been functionally validated in primary cells. Here we target 426 genes previously involved in the HIV life cycle through protein interaction studies for CRISPR-Cas9-mediated knockout in primary human CD4+ T cells to systematically assess their functional role in HIV replication. We achieve an efficient knockout (>50% of alleles) in 364 of the target genes and identify 86 candidate host factors that alter HIV infection. 47 of these factors were validated by multiplex gene editing in independent donors, including 23 factors with restrictive activity. Both gene editing efficiency and HIV-1 phenotypes correlate very well among unrelated donors. Importantly, functional roles in HIV replication have not been described for more than half of these factors, opening numerous new avenues for understanding HIV biology. These data further suggest that datasets on the protein-protein interaction between host and pathogen provide an enriched source of candidates for the discovery of functional host factors and provide an improved understanding of the mechanics of HIV replication in primary T cells.

Share.

Comments are closed.