1. DVD Molecular Epidemiology, Characterization and Immunology of Rotaviruses and Other Agents of Viral Gastroenteritis
J.R. Gentsch, B. Jiang
Rotaviruses are the most important etiologic agents of severe gastroenteritis in children; thus, development of an effective vaccine against rotavirus is a public health priority. The Centers for Disease Control and Prevention's rotavirus laboratory within the Gastroenteritis and Respiratory Viruses Laboratory Branch provides research opportunities in a wide range of areas such as the effect of genetic variation of circulating strains on vaccine efficacy, molecular epidemiology of rotavirus serotypes, development of molecular diagnostic methods, molecular characterization of prevalent strains by means of techniques such as sequencing, PCR and probe hybridization, research and development of live and inactivated rotavirus vaccines, molecular pathogenesis and immunity in humans and animal models. Other projects include epidemiology and characterization of viral agents like adenoviruses and picobirnaviruses.
Westerman, L., H. McClure, B. Jiang, J. Almond, R.I. Glass. 2005. Serum IgG mediates mucosal immunity against rotavirus infection. Proc. Natl. Acad. Sci. USA 102: 7268-7273.
Banyai, K., A. Bogdan, P. Kisfali, P. Molnar, I. Mihaly, B. Melegh, V. Martella, J. R. Gentsch, G. Szucs. 2007. Emergence of serotype G12 rotaviruses, Hungary. Emerging Infectious Diseases 13:916-9.
Wang, Y., P. Dennehy, H. Keyserling, K. Tang, J.R. Gentsch, R.I. Glass, B. Jiang. 2007. Rotavirus infection alters peripheral T-cell homeostasis in children with acute diarrhea. Journal of Virology 81: 3904-3912.
Moon SS, Wang Y, Shane AL, Nguyen T, Ray P, Dennehy P, Baek LJ, Parashar U, Glass RI, Jiang B. 2010. Inhibitory Effect of Breast Milk on Infectivity of Live Oral Rotavirus Vaccines. Pediatr Infect Dis J. 29: 919-923.
Payne DC, Edwards KM, Bowen MD, Keckley E, Peters J, Esona MD, Teel EN, Kent D, Parashar UD, Gentsch JR. 2010. Sibling transmission of vaccine-derived rotavirus (RotaTeq) associated with rotavirus gastroenteritis. Pediatrics. 125: e438-41.
2. DVD Molecular Epidemiology and Characterization of Norovirus Infection
Viral gastroenteritis is one of the most common illnesses worldwide and a major public health problem for the young and the elderly. Among a diverse group of viruses associated with acute gastroenteritis, noroviruses are the most important cause in all age groups and an increasing number of studies indicate that these viruses are second only to rotavirus in children younger than 5 year of age with severe diarrhea. The National Calicivirus laboratory at CDC has opportunities available to 1) study the biology and host-virus interactions to noroviruses, 2) study the immune response and genetic susceptibility to noroviruses, 3) characterize, develop and refine diagnostic assays for viruses newly associated with gastroenteritis, and 4) study potency of disinfections against noroviruses and study their mechanism. 5) design and assay the antiviral activity of small compounds against norovirus.Laboratory methods currently in use include realtime PCR, probe hybridization, immunofluorescence enzyme immunoassay, and confocal microscopy, nucleotide sequencing and phylogenetic analysis, cloning, protein expression and cell culture using conventional as well as 3-D culture methods.
Vinjé, J., R.A. Hamidjaja, and M.D. Sobsey. 2004. Development and application of a capsid VP1 (region D) based reverse transcription PCR assay for genotyping of genogroup I and II noroviruses. J Virol Methods. 116(2):109-17.
Zheng, D.P., T. Ando, R.L. Fankhauser, R.S. Beard, R.I. Glass, S.S. Monroe. 2006. Norovirus classification and proposed strain nomenclature. Virology. 346(2):312-23.
Blanton, L.H., S.M. Adams, R.S. Beard, G. Wei, S.N. Bulens, M.A. Widdowson, R.I. Glass, S.S. Monroe. 2006 Molecular and epidemiologic trends of caliciviruses associated with outbreaks of acute gastroenteritis in the United States, 2000-2004. J Infect Dis. Feb 1;193(3):413-21.
Cannon, J.L., E. Papafragkou, G.W. Park, J. Osborne, L.A. Jaykus and J. Vinjé. 2006. Surrogates for the study of norovirus stability and inactivation in the environment: A comparison of murine norovirus and feline calicivirus. J Food Prot. 69(11):2761-5.
Lindesmith LC, Donaldson EF, LoBue AD, Cannon JL, Zheng DP, Vinjé J, Baric RS. 2008. Mechanisms of GII.4 Norovirus Persistence in Human Populations. PloS Med. 5(2): e31
3. DVD Molecular Biology: Pathogenesis of Measles Virus Infections
P.A. Rota, W.J. Bellini
Vaccination programs have dramatically reduced the incidence of measles in many countries. In fact, indigenous transmission of measles has been eliminated in the entire Western Hemisphere since 2000. In contrast, measles remains a major problem in developing countries, and as many as 180,000 children die annually as a result of measles-associated illnesses. Research within the Measles, Mumps, Rubella and Herpes Viruses Laboratory Branch is committed to achieving a better understanding of protective immunity to and pathogenesis of measles virus infections as well as assessing the genetic and antigenic variation of wild-type measles viruses and vaccine strains. The long-term goals of the Branch are improved measles vaccines and diagnostic reagents and improved molecular epidemiologic techniques that will contribute to global measles control efforts. Current projects include molecular/genetic analysis of wild-type strains of measles viruses in order to trace the pathways of transmission of measles infections, comparison of the immune response elicited by vaccine versus wild-type viruses, evaluation of measles virus replication, and creation of improved measures of protective immunity, including development of state-of-the-art diagnostic assays for laboratory and field use. Novel mechanisms for administering measles vaccine are also being evaluated. Applicants are invited to contact the preceptors to discuss research proposals dealing with any aspect of the genetics, biology, or immunology of measles.
Bankamp, B., Takeda, M., Zhang, Y., Xu, W. & Rota, P. A. (2011). Genetic characterization of measles vaccine strains. J Infect Dis 204 Suppl 1, S533-548.
Bellini, W. J. & Rota, P. A. (2011). Biological feasibility of measles eradication. Virus Res 162, 72-79.
Lin, W. H., Griffin, D. E., Rota, P. A., Papania, M., Cape, S. P., Bennett, D., Quinn, B., Sievers, R. E., Shermer, C., Powell, K., Adams, R. J., Godin, S. & Winston, S. (2011). Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques. Proc Natl Acad Sci U S A 108, 2987-2992.
Rota, P. A., Brown, K., Mankertz, A., Santibanez, S., Shulga, S., Muller, C. P., Hubschen, J. M., Siqueira, M., Beirnes, J., Ahmed, H., Triki, H., Al-Busaidy, S., Dosseh, A., Byabamazima, C., Smit, S., Akoua-Koffi, C., Bwogi, J., Bukenya, H., Wairagkar, N., Ramamurty, N., Incomserb, P., Pattamadilok, S., Jee, Y., Lim, W., Xu, W., Komase, K., Takeda, M., Tran, T., Castillo-Solorzano, C., Chenoweth, P., Brown, D., Mulders, M. N., Bellini, W. J. & Featherstone, D. (2011b). Global distribution of measles genotypes and measles molecular epidemiology. J Infect Dis 204 Suppl 1, S514-523.
Hoang, V., Tripp, R. A., Rota, P. & Dluhy, R. A. (2010). Identification of individual genotypes of measles virus using surface enhanced Raman spectroscopy. Analyst 135, 3103-3109.
Bankamp, B., Fontana, J. M, Bellini, W. J., Rota, P. A. 2008. Adaptation to cell culture induces functional differences in measles virus proteins. Virology J. 5:139.
Sleeman, K, DA. Stein, A Tamin, M Reddish, PL. Iversen and PA. Rota. (2009) Inhibition of measles virus infections in cell cultures by peptide-conjugated morpholino oligomers. Virus Res. 140(1-2):49-56.
Bankamp, B., Hodge, G., McChesney, M. B., Bellini, W. J., and Rota, P. A. (2008). Genetic changes that affect the virulence of measles virus in a rhesus macaque model. Virology 373(1), 39-50.
Fontana, J. M., Bankamp, B., Bellini, W. J., and Rota, P. A. (2008). Regulation of interferon signaling by the C and V proteins from attenuated and wild-type strains of measles virus. Virology 374(1), 71-81.
4. DVD Immunology, Pathogenesis, and Molecular Virology of Mumps Virus Infection
C. J. Hickman, W. J. Bellini
Following introduction of a second routine dose of MMR in 1989 the incidence of mumps dropped dramatically from >16 cases/100,000 to <1/1,000,000 per year. In 2006, however, the US experienced the largest mumps outbreak in 20 years (>5000cases). The highest attack rate was reported among persons aged 18-24 years of age, many of whom were college or university students who had been vaccinated with 2 doses of MMR. High attack rates among highly vaccinated young adults in this outbreak raised concerns about mumps vaccine failure. Research within the Mumps Virus Team of the Measles, Mumps, Rubella and Herpesvirus Branch is directed at developing a better understanding of the protective immune response to mumps as well as assessing genetic and antigenic variation of mumps viruses and vaccine strains and developing diagnostic assays and strategies to detect mumps illness in highly vaccinated populations. Potential projects include the development of serological assays or direct detection methods for mumps (nucleic acid based and antigen based) and the analysis of humoral and cellular immune responses in vaccinees and those with natural infection to characterize the immune response to mumps and identify risk factors for susceptibility
5. DVD Molecular Virology and Immunology of Rubella Virus Infection
J. P. Icenogle, W. J. Bellini
The overall objectives of this research are to better understand the pathology of congenital rubella virus infection and the epidemiology and molecular epidemiology of rubella virus infection worldwide. These overall objectives are in part determined by the CDC effort in measles control and elimination since some suspect measles cases are actually rubella. The projects to be studied are flexible within the general areas of the molecular virology and immunology of rubella virus infection, provided the projects can potentially facilitate progress on the overall objectives. Examples of acceptable projects include studies of early events in rubella virus RNA replication and long term immunologic consequences of congenital rubella syndrome. The rubella virus laboratory works collaboratively with CDC public health programs concerned with congenital rubella syndrome and with other rubella virus laboratories
6. DVD Pathogen Discovery
In a significant fraction of cases of serious disease, the etiology remains unknown. In addition, infectious agents have been proposed to play a role in the etiologies of type 1 insulin-dependent diabetes, mellitus, myocarditis, and other chronic diseases. Furthermore, newly emerging pathogens or‘outbreaks’pose constant threats to public health. The main goal of the CDC Pathogen Discovery Program is to develop broadly reactive reagents and assays to enhance our ability to rapidly identify and classify new infectious agents associated with human disease, and to systematically apply these new methods to the testing of specimens from cases of serious disease of unknown etiology. Opportunities are available to: i) develop consensus degenerate PCR methods for the broad-specificity detection of new members of known virus families. ii) develop antibody-assisted protein mass spectrometry and genomic identification to identify the pathogen markers associated with human disease.iii) develop and evaluate high throughput metagenomic sequencing in combination of background subtraction as a more generic approach of detecting new infectious agents. iv) apply these new methods to the testing of patient specimens from unknown outbreaks and human diseases.
Suxiang Tong , Jatinder Singh , Susan Ruone , Charles Humphrey , Cyril C. Y. Yip , Susanna K. P. Lau ,Larry J. Anderson , and Taranjit Kaur Identification of Adenoviruses in Fecal Specimens from Wild Chimpanzees ( Pan trogylodytes schweinfurthii ) in Western Tanzania The American Society of Tropical Medicine and Hygiene May 82(5), 2010, pp. 967–970.
Yiming Ye, Eng-Chun Mar, Suxiang Tong*, Scott Sammons, Sunan Fang,Larry J. Anderson, Dongxia Wang1* Application of Proteomics Methods for Pathogen Discovery. Journal of Virological Methods. 2010 January, 163(1):87-95.
Stacy R. Finkbeiner, Yan Li, Susan Ruone, Christina Conrardy, Nicole Gregoricus, Denise Toney,Herbert W. Virgin, Larry J. Anderson, Jan Vinje´,David Wang, and Suxiang Tong. Identification of a Novel Astrovirus (Astrovirus VA1) Associated with an Outbreak of Acute Gastroenteritis. Journal of Virology Oct. 2009, 83(20)
S. Tong, C. Conrardy, S. Ruone, I. Kuzmin, X. Guo, Y.Tao, M. Niezgoda. L. Haynes, B. Agwanda, R.F. Breiman, L.J. Anderson, and C.E. Rupprecht Detection of novel SARS-like and other coronaviruses in bats from Kenya Emerg Infect Dis. 2009 Mar;15(3)
Suxiang Tong, Shur-Wern Wang Chern, Yan Li, Mark A. Pallansch, and Larry J. Anderson. Sensitive and Broadly Reactive Reverse Transcription-PCR Assays to Detect Novel Paramyxoviruses Journal of Clinical Microbiology Aug. 2008, 46 (8); 2652-2658.