Infections by human cytomegalovirus, such as CMV retinitis, account for one of the most important AIDS-associate opportunistic complications. Moreover, HCMV infections are also one of the most common causes of oral diseases associated with AIDS patients. HCMV infections in immunocompromised patients may produce oral lesions and painful ulcers and erosions have been reported on lips, tongue, and buccal mucosa. Salivary glands are a major source of persistent virus and have been shown to be a site for CMV latent infections. Viruses in saliva that are shed from infected salivary glands are believed to be one of the major sources for oral infections as well as for horizontal transmission. Understanding the mechanism of CMV infection in salivary glands as well as other parts of the oral cavity will provide insight into developing new drugs and novel strategies for treatment and prevention of CMV-associated oral diseases. Using murine cytomegalovirus as a model system, the proposed study is to identify the viral genes required for CMV replication in salivary glands and to study the functions of these viral determinants in supporting CMV infections in the oral cavity. The applicant has recently generated a pool of MCMV mutants that contain a transposon sequence and has isolated a viral mutant that was defective in replication in the salivary glands. In the proposed research, animals will be infected with viral mutants through direct inoculation to the salivary glands and those that are defective in replicating in the salivary glands will be isolated. Characterization of these mutants will be carried out to identify the genes that are mutated by the transposon insertion and their growth characteristics in tissue culture and in animals will be determined. Finally, the molecular mechanisms of how the identified viral determinants function in supporting MCMV infections in salivary glands will be studied. These studies will lead to the identification of viral genes required for CMV replication in salivary glands and the investigations of the functions of these genes in CMV infections of the oral cavity. Moreover, the results will provide insights into the mechanism of CMV pathogenesis and the development of novel strategies for treatment and prevention of CMV systemic infections as well as infections in the oral cavity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE014145-03
Application #
6634709
Study Section
Special Emphasis Panel (ZDE1-YA (07))
Program Officer
Lunsford, Dwayne
Project Start
2001-03-01
Project End
2005-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2003
Total Cost
$244,776
Indirect Cost
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
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
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
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
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