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The different strains of the human immunodeficiency virus (or HIV) can infect a variety of cells in the human body. When a cell senses being attacked, it can defend itself using molecules called restriction factors, which are created under the control of a signal known as interferon.
Researchers have already identified several restriction factors, using techniques that are relatively laborious and time-consuming, but many questions remain about these proteins. Here, Ohainle et al. created a new method to screen for restriction factors; by harnessing the CRISPR/Cas9 technique, HIV was tricked into revealing its own weaknesses. The method allowed Ohainle et al. to make precise, targeted changes to thousands of genes that are turned on by interferon, and deactivate them. The experiments revealed that HIV multiplied better in human cells in which several specific genes had been neutralized. This suggests that these genes encode restriction factors that are activated by interferon to combat HIV. The combined action of a few of these proteins can fight the virus, even if it cannot completely eradicate it. Further experiments found that a different, but overlapping set of restriction factors defended cells against a different strain of HIV.
The method developed by Ohainle et al. is a useful tool to identify new restriction factors. By dissecting the role of these proteins in keeping different HIV strains under control, we may understand how the virus has become dangerous for humans by evading some of these defenses. Ultimately, this could help with finding better ways to fight this deadly disease.