Gene Editing could destroy latent viruses in the human body like herpes







PLOS – CRISPR/Cas9-Mediated Genome Editing of Herpesviruses Limits Productive and Latent Infections

Viruses that can establish a latent relationship with the host are capable of causing disease. Examples of viruses include the Herpes Simplex Virus 1 (also dubbed HSV 1) and retroviruses . The latter group of viruses includes the Human Immunodeficiency Viruses (HIVs ) that are the most likely cause of acquired immunodeficiency syndrome (AIDS ).


Herpesviruses infect the majority of the human population and can cause significant morbidity and mortality. Herpes simplex virus (HSV) type 1 causes cold sores and herpes simplex keratitis, whereas HSV-2 is responsible for genital herpes. Human cytomegalovirus (HCMV) is the most common viral cause of congenital defects and is responsible for serious disease in immuno-compromised individuals. Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a broad range of malignancies, including Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s disease, and post-transplant lymphomas. Herpesviruses persist in their host for life by establishing a latent infection that is interrupted by periodic reactivation events during which replication occurs. Current antiviral drug treatments target the clinical manifestations of this productive stage, but they are ineffective at eliminating these viruses from the infected host. Here, we set out to combat both productive and latent herpesvirus infections by exploiting the CRISPR/Cas9 system to target viral genetic elements important for virus fitness. We show effective abrogation of HCMV and HSV-1 replication by targeting gRNAs to essential viral genes. Simultaneous targeting of HSV-1 with multiple gRNAs completely abolished the production of infectious particles from human cells. Using the same approach, EBV can be almost completely cleared from latently infected EBV-transformed human tumor cells. Our studies indicate that the CRISPR/Cas9 system can be effectively targeted to herpesvirus genomes as a potent prophylactic and therapeutic anti-viral strategy that may be used to impair viral replication and clear latent virus infection.

Author Summary

Herpesviruses are large DNA viruses that are carried by almost 100% of the adult human population. Herpesviruses include several important human pathogens, such as herpes simplex viruses (HSV) type 1 and 2 (causing cold sores and genital herpes, respectively), human cytomegalovirus (HCMV; the most common viral cause of congenital defects, and responsible for serious disease in immuno-compromised individuals), and Epstein-Barr virus (EBV; associated with infectious mononucleosis and a wide range of malignancies). Current antiviral drug treatments are not effective in clearing herpesviruses from infected individuals. Therefore, there is a need for alternative strategies to combat these pathogenic viruses and prevent or cure herpesvirus-associated diseases. Here, we have assessed whether a direct attack of herpesvirus genomes within virus-infected cells can inactivate these viruses. For this, we have made use of the recently developed CRISPR/Cas9 genome-engineering system to target and alter specific regions within the genome of these viruses. By targeting sites in the genomes of three different herpesviruses (HSV-1, HCMV, and EBV), we show complete inhibition of viral replication and in some cases even eradication of the viral genomes from infected cells. The findings presented in this study open new avenues for the development of therapeutic strategies to combat pathogenic human herpesviruses using novel genome-engineering technologies.

SOURCES- New Scientist, PLOS