This 1997 review article examines the molecular biology of caliciviruses, a family of human and animal pathogens that gained international attention following the 1995 escape of rabbit hemorrhagic disease virus (RHDV) from experiments in Australia. The authors synthesize major advances made during the 1990s in understanding calicivirus structure and genetics. Caliciviruses possess a characteristic 7.5 kb positive-sense RNA genome with polyadenylated, single-stranded molecules. Key structural features include 40-50 nm icosahedral virions with cup-shaped surface depressions visible in electron microscopy. The authors describe two distinct genome organizations: one exemplified by feline calicivirus (FCV) with three separate open reading frames, and another in RHDV where non-structural and structural proteins form a single giant polyprotein. Complete genome sequences were determined for FCV, RHDV, human enteric small round structured viruses, and human caliciviruses. The review details how calicivirus non-structural proteins, including a 3C-like protease and RNA-dependent RNA polymerase, are processed from larger polyprotein precursors through specific proteolytic cleavage events. Phylogenetic analysis based on RNA polymerase sequences reveals subdivisions into distinct calicivirus groups with different biological and clinical properties, suggesting evolutionary relationships to picornaviruses.

Key findings

• Caliciviruses contain a 7.5 kb positive-sense RNA genome encoding either three separate open reading frames (FCV-like) or a single giant polyprotein (RHDV-like) depending on the virus genus
• Complete genome sequences were obtained for multiple caliciviruses including FCV, RHDV, EBHSV, human SRSVs, and human caliciviruses, revealing conserved repeated sequence motifs at the 5' termini of genomic and subgenomic RNAs
• Calicivirus virions are 40-50 nm icosahedral particles with 32 cup-shaped surface depressions containing T=3 icosahedral symmetry and composed of capsid protein dimers
• A 3C-like serine protease cleaves the non-structural polyprotein at specific glutamic acid-containing dipeptide sites, releasing functional proteins in a cascade similar to picornaviruses
• Phylogenetic analysis of RNA polymerase sequences identifies distinct calicivirus groups corresponding to different viral species and disease phenotypes, suggesting evolutionary relationships to the Picornaviridae family