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.