Molecular Biology of Caliciviruses: Cellular and Viral Proteins Involved in the Establishment of the Infection

Human noroviruses (HuNoV), classified in the family Caliciviridae, are increasingly recognized as a leading cause of acute gastroenteritis worldwide, affecting people of all ages; children and the elderly are the most affected. Outbreaks occur in both low- and high-income countries, but hospitalization and deaths are more frequent in children from developing countries. HuNoV has been challenging to propagate conveniently in vitro; however, cultivable surrogate caliciviruses such as murine norovirus (MNV) and feline calicivirus (FCV) have been used to study the biology and pathogenesis of these fastidious viruses and will be the focus of this chapter. Caliciviruses cause different diseases in a wide variety of vertebrates; they are spherical, non-enveloped, 35–40 nanometers (nm) in diameter, with a single-stranded positive polarity genomic RNA of approximately 7.3–7.5 nucleotides (nt) in length, commonly containing three open reading frames (ORF). ORF1 encodes a polyprotein that is processed in 6 nonstructural (NS) proteins, while ORF 2 and 3 encode the major (VP1) and the minor (VP2) capsid proteins, respectively. These two proteins are translated from a subgenomic (sg) RNA late during infection. The calicivirus replicative cycle occurs in the cytoplasm of the infected cells and depends on cellular factors and the induction of apoptosis for virus release and spread into the host; both are aspects of major interest in the field. Evidence from our laboratory and others using both MNV and FCV have shown the dependency on cellular proteins for efficient viral replication. Moreover, viral proteins involved in apoptosis induction have been identified. Recognizing viral and cellular molecules involved in calicivirus replication may help to develop antiviral therapies, either by impeding the activity of viral components or temporarily blocking cell processes on which the virus depends for its replication.