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Title:   Author  item
                                            Richards, Gary
  Submitted to: Food and Environmental Virology
                                    Publication Type: Review Article
                                    Publication Acceptance Date: 11/16/2011
                                    Publication  Date: 3/2/2012
                                    Citation: Richards, G.P. 2012. Critical review of norovirus surrogates in food safety research: rationale for considering volunteer studies. Food and Environmental Virology. 4:6-13.Interpretive Summary: Human norovirus (NoV) is the principle cause of foodborne illness.  Unlike most foodborne viruses, NoV cannot be grown in cell culture, thus alternate means must be used to detect the presence of virus particles.  Molecular methods have been developed, but they only detect the presence of virus particles and are currently unable to differentiate between infectious and inactivated viruses.  In an effort to better understand mechanisms for the inactivation of NoV, related viruses known as surrogate viruses are often used.  Feline calicivirus and murine norovirus are two surrogates that have been employed over the past 20 years; however, it has become clear that these viruses do not always mimic the response of NoV to inactivation treatments.  Considerable research funding has been devoted to surrogate research, but little benefit has been derived since the results are only speculative.  Human volunteer studies are needed to validate research on surrogates and to better define the ability of processing interventions to inactivate NoV.  We recently conducted a volunteer study on the effects of high pressure processing to eliminate NoV in oysters in which we determined that NoV is more resistant to the effects of high pressure than the feline calicivirus or murine norovirus surrogates.  Our work demonstrates the benefit of conducting clinical trials and the inadequacies of surrogate studies.  Thus, an emphasis in research on human volunteer studies is needed in order to obtain definitive information on the effectiveness of processing interventions for NoV inactivation.  Volunteer studies are performed in hospitals under closely controlled conditions to minimize risks to the participants.  Clinical trials to determine the ability of disinfectants and food and water processing strategies to eliminate NoV are essential if we are to reduce the incidence of NoV outbreaks within the population.
                                Technical Abstract: The inability to propagate human norovirus (NoV) or to clearly differentiate infectious from noninfectious virus particles have led to the use of surrogate viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are propagatable in cell culture.  The use of surrogates is predicated upon the assumption that they generally mimic the viruses they represent; however, studies are proving this concept invalid.  In direct comparisons between FCV and MNV, their susceptibility to temperatures, environmental and food processing conditions, and disinfectants are dramatically different.  Differences have also been noted between the inactivation of NoV and its surrogates, thus questioning the validity of surrogates.  Considerable research funding is provided globally each year to conduct surrogate studies on NoVs; however, there is little demonstrated benefit derived from these studies in regard to the development of virus inactivation techniques or food processing strategies.  Human challenge studies are needed to determine which processing techniques are effective in reducing NoVs in foods.  A major obstacle to clinical trials on NoVs is the perception that such trials are too costly and risky, but in reality, there is far more cost and risk in allowing millions of unsuspecting consumers to contract NoV illness each year, when practical interventions are only a few volunteer studies away.  A number of clinical trials have been conducted, providing important insights into NoV inactivation.  A shift in research priorities from surrogate research to volunteer studies is essential if we are to identify realistic, practical, and scientifically valid processing approaches to improve food safety.


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