Human monoclonal antibodies able to neutralize live human norovirus GII.4 Sydney 2012—the predominant strain responsible for recent outbreaks—are reported in the December issue of Gastroenterology. Researchers analyzed these antibodies and identified the neutralizing epitopes, providing insight into the human immune response to this deadly virus.
Human noroviruses are the major cause of epidemic and sporadic acute gastroenteritis, due to their low infectious dose, environmental stability, high levels of shedding, and prolonged shedding even after symptoms have resolved. Noroviruses cause an average 19–21 million cases of infection and 570–800 deaths in children younger than 5 years each year in the United States, although they infect people of all ages. Even though infection is usually acute and self-limited, disease can become life threatening in young, old and immunocompromised people.
The extreme antigenic diversity of strains poses challenges to developing antibodies or vaccines to prevent noroviruses-associated disease. Noroviruses are classified into 7 different genogroups (genogroups [G] I–VII), and at least 41 different genotypes. Viruses from G1 and the rapidly evolving GII account for nearly all human infections. The human norovirus genome contains 3 open-reading frames (ORFs). ORF1 encodes nonstructural proteins, whereas ORF2 and ORF3 encode the major and minor capsid proteins, respectively.
Noroviruses could not previously be cultivated in cell culture, but the VP1 and VP2 protein sequences could be expressed using a baculovirus expression system to produce human noroviruses virus-like particles (VLPs). These VLP reagents have facilitated the study of norovirus evolution, antigenicity, and the emergence of strains.
In the journal Clinical Gastroenterology and Hepatology, Shintaro Sato et al report propagation of human norovirus (the the GII.3, GII.4, GII.6, and GII.17 genotypes) in human induced pluripotent stem cell-derived intestinal epithelial cells.
Since the mid-1990s, viruses from GII genotype 4 (GII.4) have caused most outbreaks, with new strains emerging every 2–3 years. In 2012, the GII.4 Sydney strain emerged and began spreading globally—it has continued to predominate among circulating strains. However, the molecular basis for antibody-mediated recognition of these strains and their mechanisms of action are not well characterized.