Areas of Interest
- Virus-host interactions
- Translational control, replication and assembly of RNA viruses
- miRNA-mediated gene regulation
- RNA granules
Infection with HCV is the foremost cause of liver disease in the United States. The current anti-HCV treatments are insufficient, and a protective vaccine is not available. The Pager laboratory is fascinated by virus-host interactions. We are particularly interested in how Hepatitis C virus (HCV) interacts with and manipulates host mRNA metabolism. For example: to synthesize viral proteins, HCV uses a RNA element known as an internal ribosome entry site or IRES, at the start of the viral genome to recruit cellular ribosomes and a subset of translation factors. Furthermore, HCV uniquely interacts with the liver-specific microRNA miR-122 to maintain the levels of viral RNA. We recently discovered that a number of cellular factors found in RNA granules are critical for HCV gene expression, and that the virus specifically recruits these factors to sites where the virus assembles. Curiously many of these RNA granule factors are involved in microRNA-mediated gene regulation, mRNA storage and mRNA degradation. Our current research focuses on understanding how and why HCV exploits these factors for virus gene expression. We use methods in virology, biochemistry, RNA biology, cell biology and microscopy to determine the importance and function of these factors at each step in the HCV lifecycle; RNA granule-HCV interactions; and the protein and RNA modifications that occur during HCV infection. By understanding the HCV lifecycle and virus-host interactions our ultimate goal is identify and develop novel anti-HCV targets.
- Pager CT, Schütz S, Abraham TM, Luo G, Sarnow P. 2013. Modulation of Hepatitis C virus RNA abundance and virus release by dispersion of Processing bodies and enrichment of stress granules. Virology. 435: 472-484.
- Yip L, Creusot RJ, Pager CT, Sarnow P, Fathman CG. Transcriptional and translational control of ectopic peripheral tissue antigen expression by Deaf1. Journal of Molecular Cell Biology. 5(2):99-110.
- Popa A, Pager CT, Dutch RE. 2011. C-terminal tyrosine residues modulate the fusion activity of the Hendra virus fusion protein. Biochemistry. 50: 945-952.
- Sun C, Pager CT, Sarnow P, Luo G, Cate J. 2010. The role of interactions between DDX3X and Hepatitis C virus core-derived peptides in the hepatitis C viral life cycle. PLoS One. 5.pii. e12826.
- Fuchs G, Pager CT. 2010. HCV and the interaction with miR-122 in the liver. In “RNA interference and viruses: Current innovations and future trends” Martínez MA, eds. Casiter Academic Press. Chapter 6.
- Pager CT, Wehner KA, Fuchs G, Sarnow P. 2009. MicroRNA-mediated gene silencing. In “Progress in Molecular Biology and Translational Science” Hershey JWB, eds. Elsevier. Vol 90: 187-210.
- Pager CT, Craft WW, Patch J, Dutch RE. 2006. A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L. Virology. 346: 251-257.
- Pager CT and Dutch RE. 2005. Cathepsin L is involved in proteolytic processing of the Hendra virus fusion protein. Journal of Virology. 79: 12714-12720.
- Carter JR, Pager CT, Fowler SD, Dutch RE. 2005. The role of N-linked glycosylation of the Hendra virus fusion protein. Journal of Virology. 79: 7922-7925.
- Pager CT, Wurth MA, Dutch RE. 2004. Subcellular localization and calcium and pH requirements for the proteolytic processing of the Hendra virus fusion protein. Journal of Virology. 78: 9154-9163.
- Rucker AL, Pager CT, Campbell MN, Qualls JE, Creamer TP. 2003. Host-guest scale of left-handed polyproline II helix formation. Proteins. 53: 68-75.
- Steele AD, Peenze I, de Beer MC, Pager CT, Yeats J, Potgieter N, Ramsaroop U, Page NA, Mitchell JO, Geyer A, Bos P, Alexander JJ. 2003. Anticipating rotavirus vaccines: epidemiology and surveillance of rotavirus in South Africa. Vaccine. 21: 354-360.
- Pager CT, Steele AD. 2002. Astrovirus-associated diarrhea in South African adults. Clinical Infectious Diseases. 35: 1452-1453.
- Pennap G, Pager CT, Peenze I, de Beer MC, Kwaga JK, Ogalla WN, Umoh JU, Steele AD. 2002. Epidemiology of astrovirus infection in Zaria, Nigeria. Journal of Tropical Pediatrics. 48: 98-101.
- Armah GE, Pager CT, Asmah RH, Anto R, Oduro R, Binka F, Steele AD. 2001. Prevalence of unusual human rotavirus strains in Ghanaian children. Journal of Medical Virology. 63: 67-71.
- Trabelsi A, Peenze I, Pager C, Jeddi M, Steele D. 2000. Distribution of rotavirus VP7 serotypes and VP4 genotypes circulating in Sousse, Tunisia, from 1995 to 1999: emergence of natural human reassortants. Journal of Clinical Microbiology. 38: 3415-3419.
- Pennap G, Peenze I, de Beer M, Pager CT, Kwaga JKP, Ogalla WN, Umoh JU, Steele AD. 2000. VP6 subgroup and VP7 serotype of human rotavirus in Zaria, Northern Nigeria. Journal of Tropical Pediatrics. 46: 344-347.
- Pager CT, Alexander JJ, Steele. 2000. South African G4P asymptomatic and symptomatic neonatal rotavirus strains differ in their NSP4, VP8*, and VP7 genes. Journal of Medical Virology. 62: 208-216.
- Pager C, Steele D, Gwamanda P, Driessen M. 2000. A neonatal death associated with rotavirus infection: detection of rotavirus dsRNA in the cerebrospinal fluid. South African Medical Journal. 90: 364-365. (Letter).
- Steele AD, Parker SP, Peenze I, Pager CT, Taylor MB, Cubitt WD. 1999. Comparative studies of human rotavirus serotype G8 strains recovered in South Africa and the United Kingdom. Journal of General Virology. 80: 3029-3034.