Oral infection represents an important route of human cytomegalovirus (HCMV) transmission. HCMV infection is also among the most common causes of oral diseases associated with AIDS patients. Understanding the mechanism of HCMV infection in oral mucosa as well as other parts of the oral cavity will provide insight into developing new drugs and novel strategies for treatment and prevention of HCMV-associated oral diseases. The objective of the proposed research is to study HCMV chromatin modifications and their roles in viral infection in oral mucosa. Recent studies in our laboratory have shown that epigenomic modifications, including histone tail changes by methylation, have been found in HCMV chromatin in human primary oral cell and tissue cultures. Furthermore, preliminary studies have suggested that specific viral proteins affect the epigenetic modifications of viral chromatin, and that some of these modifications specifically modulate the expression of viral gene expression required for HCMV productive infection. In the initial part of the proposed study, we will screen a collection of HCMV mutants with deletion of a single viral open reading frame (ORF) to isolate mutants that exhibit altered viral chromatin modifications and to identify viral determinants important for specific modifications of HCMV chromatin in oral mucosa. Experiments will then be carried out to study the roles of the identified modifications of viral chromatin in regulating viral gene transcription and supporting viral infection in oral cells. Furthermore, experiments will also be carried out to investigate how the viral determinants modulate specific HCMV chromatin modifications by interacting with the epigenetic remodeling complexes in order to facilitate HCMV infection in oral cavity. These studies will lead to the identification of viral determinants important for HCMV chromatin modifications and for viral infection in oral mucosa. Furthermore, our studies will investigate how HCMV replicates in oral mucosa and how HCMV-encoded determinants function to modulate HCMV chromatin modifications and support viral infection in oral mucosa. Our results will provide insight into the mechanism of HCMV infection in oral mucosa and facilitate the development of novel strategies for treatment and prevention of the transmission as well as infection of HCMV in oral cavity.

Public Health Relevance

The objective of the proposed research is to study the roles of viral chromatin modifications in oral infections of human cytomegalovirus, a leading cause of viral congenital infections and one of the most common opportunistic pathogens encountered in AIDS patients. Our study will facilitate the development of novel approaches and therapeutic agents for the prevention and treatment of HCMV infections in oral cavity.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDE1)
Program Officer
Rodriguez-Chavez, Isaac R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
Schools of Public Health
United States
Zip Code
Francis, Stephen Starko; Wallace, Amelia D; Wendt, George A et al. (2017) In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia. Blood 129:1680-1684
Li, Wei; Sheng, Jingxue; Xu, Mengqiong et al. (2017) Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences. Mol Ther Nucleic Acids 9:322-332
Gu, Hongwei; Zhao, Chihao; Zhang, Tianfu et al. (2017) Salmonella produce microRNA-like RNA fragment Sal-1 in the infected cells to facilitate intracellular survival. Sci Rep 7:2392
Liu, Jin; Shao, Luyao; Trang, Phong et al. (2016) Inhibition of herpes simplex virus 1 gene expression and replication by RNase P-associated external guide sequences. Sci Rep 6:27068
Pan, Chaoyun; Zhu, Dihan; Wang, Yan et al. (2016) Human Cytomegalovirus miR-UL148D Facilitates Latent Viral Infection by Targeting Host Cell Immediate Early Response Gene 5. PLoS Pathog 12:e1006007
Lei, Lei; Wang, Wenbiao; Xia, Chuan et al. (2016) Salmonella Virulence Factor SsrAB Regulated Factor Modulates Inflammatory Responses by Enhancing the Activation of NF-?B Signaling Pathway. J Immunol 196:792-802
Pan, Yi; Wang, Nan; Zhou, Zhenxian et al. (2016) Circulating human cytomegalovirus-encoded HCMV-miR-US4-1 as an indicator for predicting the efficacy of IFN? treatment in chronic hepatitis B patients. Sci Rep 6:23007
Pei, Zenglin; Jiang, Xiaohong; Yang, Zhu et al. (2015) Oral Delivery of a Novel Attenuated Salmonella Vaccine Expressing Influenza A Virus Proteins Protects Mice against H5N1 and H1N1 Viral Infection. PLoS One 10:e0129276
Yang, Zhu; Reeves, Michael; Ye, Jun et al. (2015) RNase P Ribozymes Inhibit the Replication of Human Cytomegalovirus by Targeting Essential Viral Capsid Proteins. Viruses 7:3345-60
Jiang, Xiaohong; Sunkara, Naresh; Lu, Sangwei et al. (2014) Directing RNase P-mediated cleavage of target mRNAs by engineered external guide sequences in cultured cells. Methods Mol Biol 1103:45-56

Showing the most recent 10 out of 17 publications