Abstract

Human cytomegalovirus (HCMV) causes one of the most common opportunistic infections in immunocompromised individuals, including organ transplant recipients and AIDS patients. Moreover, HCMV infections are also among the most common causes of oral diseases associated with AIDS patients, including oral lesions in gingival and buccal mucosa and xerostomia associated with impaired salivary gland function. Salivary glands are a major source of persistent virus and have also been shown to be a site for CMV latent infections. Viruses in saliva that are shed from the infected salivary glands are believed to be one of the major sources for oral infections as well as for horizontal transmission. Eliminating viral replication and infection in salivary gland is central to the control of HCMV oral transmission as well as systemic diseases associated with AIDS patients. Understanding the mechanism of CMV infections in salivary gland will provide insight into treatment and prevention of CMV-associated diseases. Using murine CMV (MCMV) infection of mice as a model system, the proposed study is to identify viral genes required for CMV replication in salivary gland and to study the functions of these viral determinants in supporting CMV infections in oral cavity. We have used a Tn-3 based transposon to develop a novel approach to construct MCMV mutants and have recently isolated two novel mutants that are attenuated in growth in salivary gland. In the proposed research, mice will be infected with viral mutants and those mutants that are defective in replicating in salivary glands will be isolated. The pathogenecity of these mutants will be studied, and the genes that are mutated will be identified. Moreover, the mechanism of how the identified viral determinants function in supporting MCMV infections in salivary gland will be investigated. These studies will identify viral determinants for infection in salivary gland and elucidate the functions of these genes in the development of CMV-associated oral diseases. Understanding the mechanism of CMV infection in salivary gland will facilitate the development of novel strategies for treatment and prevention of CMV-associated oral diseases as well as viral systemic infections.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE014145-05
Application #
6948061
Study Section
Special Emphasis Panel (ZRG1-AARR-D (02))
Program Officer
Lunsford, Dwayne
Project Start
2001-03-01
Project End
2010-03-31
Budget Start
2005-04-15
Budget End
2006-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$329,000
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Internal Medicine/Medicine
Type
Schools of Public Health
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Yang, Zhu; Mao, Guoliang; Liu, Yujun et al. (2013) Detection of the pandemic H1N1/2009 influenza A virus by a highly sensitive quantitative real-time reverse-transcription polymerase chain reaction assay. Virol Sin 28:24-35
Luo, Jun; Chen, Jun; Yang, Edward et al. (2013) Modulation of the cellular distribution of human cytomegalovirus helicase by cellular factor Snapin. J Virol 87:10628-40
Rider, Paul J; Liu, Fenyong (2012) Crosstalk between HIV and hepatitis C virus during co-infection. BMC Med 10:32
Jiang, Xiaohong; Chen, Yuan-Chuan; Gong, Hao et al. (2012) Ribonuclease P-mediated inhibition of human cytomegalovirus gene expression and replication induced by engineered external guide sequences. RNA Biol 9:1186-95
Pei, Yonggang; Fu, Wenmin; Yang, Ed et al. (2012) A Hsp40 chaperone protein interacts with and modulates the cellular distribution of the primase protein of human cytomegalovirus. PLoS Pathog 8:e1002968
Shen, Ao; Lei, Ji; Yang, Edward et al. (2011) Human cytomegalovirus primase UL70 specifically interacts with cellular factor Snapin. J Virol 85:11732-41
To, Aaron; Bai, Yong; Shen, Ao et al. (2011) Yeast two hybrid analyses reveal novel binary interactions between human cytomegalovirus-encoded virion proteins. PLoS One 6:e17796
Gong, Hao; Vu, Gia-Phong; Bai, Yong et al. (2010) Differential expression of Salmonella type III secretion system factors InvJ, PrgJ, SipC, SipD, SopA and SopB in cultures and in mice. Microbiology 156:116-27
Gong, Hao; Su, Jing; Bai, Yong et al. (2009) Characterization of the expression of Salmonella Type III secretion system factor PrgI, SipA, SipB, SopE2, SpaO, and SptP in cultures and in mice. BMC Microbiol 9:73
Kim, Kihoon; Liu, Fenyong (2007) Inhibition of gene expression in human cells using RNase P-derived ribozymes and external guide sequences. Biochim Biophys Acta 1769:603-12

Showing the most recent 10 out of 13 publications