INTRODUCTION
Norovirus (NoV) is a leading cause of epidemic non-bacterial acute gastroenteritis in children under five years and adults worldwide [1, 2]. In the United States, NoV infection is associated with an estimated 71,000 hospitalizations and 21 million total illnesses per year [3]. NoV infection is characterized by the acute onset of vomiting, diarrhea, nausea, abdominal cramps, and/or fever, which generally last for 48-72 hours. NoV transmission occurs through contaminated water, food, hands, and environmental surfaces, and person to person by the fecal-oral route [4].
The NoV genome is a linear, positive-sense, single-stranded RNA, and these viruses are classified into at least ten genogroups (GI-GX) and 49 genotypes based on the major structural protein (VP1) amino acid sequence diversity [5]. Only genogroups I (GI), GII, and GIV have been associated with human gastroenteritis. NoV GII is further divided into 22 genotypes [6]. Snow Mountain Virus (SMV) is the prototype strain of genogroup II genotype II NoV.
Human challenge studies with Norwalk virus (NV, the prototype of NoV genogroup I and genotype I) demonstrated a strong association between NV infection and secretor status as determined by the FUT2 gene [7, 8]. FUT 2 encodes an α(1,2) fucosyltransferase that is responsible for the synthesis of H antigen, and individuals with H antigen expression are considered secretor positive. Previous human challenge studies indicated that secretor-negative individuals do not become infected with NV regardless of the dose [7], but the relationship between secretor status and genogroup II NoV infection is less clear. We observed SMV infection and illness in both secretor-positive and secretor-negative subjects challenged with SMV [9]. Secretor-negative subjects are not completely protected from GII.4 infections [10].
The human challenge model has been used to study the pathogenesis and immunology of NoV infection, and the efficacy of NoV vaccine candidates. We have conducted two SMV human challenge studies, one between 2000 to 2002 with a first generation SMV inoculum [11] and the second between 2016 to 2018 with a second generation SMV inoculum [9].
The objectives of this analysis were to compare infection (defined by serum IgG conversion and/or detection of SMV RNA in stool by RT-PCR or RT-qPCR) and illness (defined by diarrhea, vomiting, and other clinical symptoms) among subjects challenged with the first SMV inoculum [11] prepared by Dolin et al. around 1980 [12] and the second SMV inoculum prepared in 2009 by Dr. Baric [9]. This analysis also examined the severity of illness and the duration of the viral shedding among human volunteers challenged with the two SMV inocula. The results from this study will contribute to our understanding of SMV infectivity and pathogenesis.