UC Berkeley

With a genome size of 230–240 kb, human cytomegalovirus (HCMV) has the largest genome in the human herpes virus family. Once the hosts are infected with HCMV, HCMV remains latent throughout the lifetime, but the latent infection can be reactivated when the host is immunocompromised. The infection symptom is mild or subclinical diseases in immunocompetent adults, but HCMV infection leads to severe, life-threatening complications in people who are immunocompromised, including AIDS patients and transplant recipients. While there’s no vaccine available for HCMV infection, understanding the nature of HCMV replication, latency, and transmission is crucial for preventing and curing the disease.

Here we discussed the relationship between various small RNAs and HCMV. In the first part of the study, we examined one viral encoded micro RNA, HCMV-mir-UL22A*, and its influence on HCMV viral infection. We investigated the mechanism of blunt-end HCMV-mir-UL22A* inhibition of HCMV viral replication. The rapid and long lasting suppression of viral replication by blunt-end HCMV-mir-UL22A* suggests blunt-end HCMV-mir-UL22A* a promising antiviral agent. Furthermore, we studied the stagger-end HCMV-mir-UL22A* in regulating host innate immune response. Stagger-end HCMV-mir-UL22A* targets innate immune sensors and facilitate HCMV evade host innate immune response during viral infection. Blunt-end HCMV-mir-UL22A* showed potential for treating CMV infection, while stagger-end HCMV-mir-UL22A* helped us understand HCMV viral innate immune evasion strategy.

In the second part of the study, we focused on applying RNA based precise gene editing technology to treat HCMV infection. Curing CMV infection requires disruption of the viral genome by novel gene editing technology. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system is a gene editing tool for the site-specific cleavage of DNA. We adapted CRISPR/Cas9 system in CMV infected cells. CRISPR/Cas9 could suppress HCMV and MCMV infection in vitro in cell model. Our study suggests CRISPR/Cas9 can potentially be applied to treat CMV infection.