Established in 2005
Kim Green, Ph.D.
Chief, Caliciviruses Section
Major Areas of Research
- Molecular epidemiology and evolution of noroviruses
- Model systems for evaluating norovirus vaccines and therapeutics
- Translational research to prevent and treat norovirus disease
Noroviruses in the Caliciviridae are a major cause of acute gastroenteritis in all age groups. The illness occurs often in settings where people are in close contact, such as families, nursing homes, hospitals, schools, camps, cruise ships, military barracks, and social gatherings. In most individuals, norovirus gastroenteritis (known commonly as “stomach flu”) resolves in two to three days. However, in patients with underlying conditions such as immunosuppression or in the very old and young, the illness can become life-threatening. There are presently no approved vaccines or specific antiviral drugs for the noroviruses, and the overall goal of this research program is to advance their development.
The current focus of our laboratory is to translate advances in norovirus research to patient care. The NIH Clinical Research Center (CRC) conducts studies that cover a broad range of medical conditions. Our work in the Caliciviruses Section has confirmed norovirus as the single most important enteric virus in patients admitted to the NIH CRC with diarrhea. Moreover, we have shown that noroviruses can be associated with chronic infection in patients with a primary or secondary immunodeficiency. In some patients, these infections are associated with recurring diarrheal disease and life-threatening malnutrition. Therapeutics are needed and we are involved in both the development and evaluation of norovirus therapies.
Our laboratory has studied the molecular epidemiology of noroviruses associated with chronic infection. We investigated whether a specific norovirus strain or strains might cause chronic infections, and whether NIH patients were exposed to the virus during visits to the NIH. We have found no evidence for hospital-acquired infections. Rather, immunocompromised individuals acquire their norovirus infection in the community through the classical routes of norovirus transmission such as person-to-person spread or swallowing the virus in contaminated food or water. Thus, it is likely that any norovirus strain has the capacity to establish a chronic infection in people with impaired immune systems. To reduce transmission of norovirus to immunocompromised individuals and other groups at higher risk from severe diarrhea, the CDC has provided excellent guidelines for the prevention of norovirus infection.
Another area of research in our laboratory is to develop experimental systems in which to study norovirus replication. Most viruses can be studied in continuous cell lines that allow the detection and quantification of infectious virus particles. However, the human noroviruses replicate poorly if at all in such cell lines. We have conducted comparative studies among diverse members of the Caliciviridae to learn common themes in calicivirus replication that may help improve our understanding of the human noroviruses. A recent discovery has given clues into how we might improve in vitro experimental systems. A new target cell for human norovirus replication was found in the small intestinal tissue of a young child who had developed severe norovirus diarrhea following transplant surgery. This cell type, called an enteroendocrine cell or EEC, was shown to be infected with norovirus. These cells play a major role in communication pathways in the gut and we are currently developing tools in the laboratory to investigate the effects of norovirus infection in these cells.
Ph.D., The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee
Dr. Green earned her Ph.D. from the University of Tennessee Center for Health Sciences in Memphis in the department of microbiology and immunology. She joined the Laboratory of Infectious Diseases in 1986 and has focused on the study of viruses associated with gastroenteritis. In recent years, her research program has addressed the role of noroviruses in human disease, with an emphasis on the development of prevention and control strategies.
- Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment in Immunocompromised Hosts (ATLANTIC): NCT04691622
- Michael Keller, Children’s National Research Institute, Washington, D.C.
- Viral Infections in Healthy and Immunocompromised Hosts: NCT01306084
- Jeffrey Cohen, Laboratory of Infectious Diseases, NIAID, NIH.
Green KY, Kaufman SS, Nagata BM, Chaimongkol N, Kim DY, Levenson EA, Tin CM, Yardley AB, Johnson JA, Barletta ABF, Khan KM, Yazigi NA, Subramanian S, Moturi SR, Fishbein TM, Moore IN, Sosnovtsev SV. Human norovirus targets enteroendocrine epithelial cells in the small intestine. Nat Commun. 2020 Jun 2;11(1):2759.
Hanajiri R, Sani GM, Saunders D, Hanley PJ, Chopra A, Mallal SA, Sosnovtsev SV, Cohen JI, Green KY, Bollard CM, Keller MD. Generation of Norovirus-Specific T Cells From Human Donors With Extensive Cross-Reactivity to Variant Sequences: Implications for Immunotherapy. J Infect Dis. 2020 Feb 3;221(4):578-588.
Bok K, Prevots DR, Binder AM, Parra GI, Strollo S, Fahle GA, Behrle-Yardley A, Johnson JA, Levenson EA, Sosnovtsev SV, Holland SM, Palmore TN, Green KY. Epidemiology of Norovirus Infection Among Immunocompromised Patients at a Tertiary Care Research Hospital, 2010-2013. Open Forum Infect Dis. 2016 Sep 8;3(3):ofw169.
Garaicoechea L, Aguilar A, Parra GI, Bok M, Sosnovtsev SV, Canziani G, Green KY, Bok K, Parreño V. Llama nanoantibodies with therapeutic potential against human norovirus diarrhea. PLoS One. 2015 Aug 12;10(8):e0133665.
Bok K, Green KY. Norovirus gastroenteritis in immunocompromised patients. N Engl J Med. 2012 Nov 29;367(22):2126-32.
The Caliciviruses Section addresses the role of human caliciviruses in human disease, with a focus on the development of prevention and control strategies for the noroviruses.