Human Norovirus: Experimental Models of Infection

Abstract

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. HuNoV infections lead to substantial societal and economic burdens. There are currently no licensed vaccines or therapeutics for the prevention or treatment of HuNoVs. A lack of well-characterized in vitro and in vivo infection models has limited the development of HuNoV countermeasures. Experimental infection of human volunteers and the use of related viruses such as murine NoV have provided helpful insights into HuNoV biology and vaccine and therapeutic development. There remains a need for robust animal models and reverse genetic systems to further HuNoV research. This review summarizes available HuNoV animal models and reverse genetic systems, while providing insight into their usefulness for vaccine and therapeutic development.

Vero Cells as a Mammalian Cell Substrate for Human Norovirus

“…This may indicate that following virus uncoating, a new infection cycle is not initiated but this has not been experimentally confirmed. Notably, a single HuNoV replication cycle has also been reported for other HuNoV replicon models [27]. A comparable attempt at infecting Vero cells did not observe g.e.…”

“…Currently, there are no licensed vaccines or approved therapeutics for HuNoV. This is related to the lack of a characterized and reproducible mammalian cell substrate, a lack of a small animal model that emulates infection and disease, and the absence of methods to properly assess vaccine efficacy or protection [25][26][27]. The most progressed HuNoV vaccine candidates are subunit vaccines generated Total RNA extracted from Vero cells infected with HuNoV at 0 h and 72 h time-points were reverse transcribed and PCR amplified using an AgPath-ID One-Step RT-PCR kit and the NK2P 2 F (+) and Cap C (−) 5 -CCTTYCCAKWTCCCAYGG [1 µM] primers to amplify a segment of the genome between the RdRp and VP1 gene sequences that spans the ORF1-2 junction [50].…”

Evaluation of the 50% Infectious Dose of Human Norovirus Cin-2 in Gnotobiotic Pigs: A Comparison of Classical and Contemporary Methods for Endpoint Estimation

“…An ideal animal model of HuNoV infection and disease would be one that can replicate the biological and clinical features associated with human disease, including the route of infection, the infective dose, the disease progression and pathogenesis, and correlates of protection [9]. Among the different models used in norovirus (NoV) research [10][11][12][13][14], gnotobiotic (Gn) pigs provide a suitable solution for studying HuNoV infection and disease, as well as for evaluating immunogenicity and protective the efficacy of novel vaccine candidates. This is attributed to the close similarity in physiology, immune development, virus binding patterns, and histo-blood group antigen (HBGA) phenotypes between pigs and humans [11].…”

Caliciviridae Other Than Noroviruses

“…*The review on Caliciviridae other than noroviruses complements the many contributions to NoV research in this Special Issue of Viruses which relate to:NoV structure [14];The molecular biology of NoV replication [15];NoV replication in the immunocompromised host [16];Factors affecting host susceptibility to NoV infection [17];In vitro propagation of NoVs [18];Innate and acquired immune responses to NoV infections [19];Molecular epidemiology of HuNoVs [20];Use of animal models of NoV infection [21];Treatment and development of antivirals [22];Vaccine development [23]. …”