Astrovirus

Astroviruses (Astroviridae) are a type of virus that was first discovered in 1975 using electron microscopes following an outbreak of diarrhea in humans. In addition to humans, astroviruses have now been isolated from numerous mammalian animal species (and are classified as genus Mamastrovirus) and from avian species such as ducks, chickens, and turkey poults (classified as genus Avastrovirus). Astroviruses are 28–35 nm diameter, icosahedral viruses that have a characteristic five- or six-pointed star-like surface structure when viewed by electron microscopy. Along with the Picornaviridae and the Caliciviridae, the Astroviridae comprise a third family of nonenveloped viruses whose genome is composed of plus-sense, single-stranded RNA. Astrovirus has a non-segmented, single stranded, positive sense RNA genome within a non-enveloped icosahedral capsid. Human astroviruses have been shown in numerous studies to be an important cause of gastroenteritis in young children worldwide. In animals, Astroviruses also cause infection of the gastrointestinal tract but may also result in encephalitis (humans and cattle), hepatitis (avian) and nephritis (avian).

This family of viruses consists of two genera, Avastrovirus (AAstV) and Mamastrovirus (MAstV).

The International Committee on Taxonomy of Viruses (ICTV) established Astroviridae as a viral family in 1995. There have been over 50 astroviruses reported, although the ICTV officially recognizes 22 species. The genus Avastrovirus comprises three species; Chicken astrovirus (Avian nephritis virus types 1–3), Duck astrovirus (Duck astrovirus C-NGB), and Turkey astrovirus (Turkey astrovirus 1). The genus Mamastrovirus includes Bovine astroviruses 1 and 2, Human astrovirus (types 1–8), Feline astrovirus 1, Porcine astrovirus 1, Mink astrovirus 1 and Ovine astrovirus 1.

Astroviruses have a star-like appearance with five or six points. Their name is derived from the Greek word "astron" meaning star. They are non-enveloped RNA viruses with cubic capsids, approximately 28–35 nm in diameter with T=3 symmetry. Human astroviruses are part of the Mammastrovirus genus and contains 8 serotypes. The human astrovirus capsid spikes have a distinct structure. The spike domain in particular has a 3-layered beta-sandwiches fold and a core, 6-stranded beta-barrel structure. The beta-barrel has a hydrophobic core. The triple-layered beta-sandwich is packed outside the beta-barrel. The spike also forms a dimer. This unique structure was found to be similar to the protein projections found on the capsid of the hepatitis E virus. The projection domain of the human astrovirus contains a receptor binding site for polysaccharides. The amino acid sequence of the astrovirus capsid protein does not have similar homology to other known viral proteins, but the closest would be hepatitis E virus.

Astroviruses infect birds and mammals through the fecal-oral route. They have a tissue tropism for enterocytes. Entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Replication follows the positive-strand RNA virus replication model. Astrovirus RNA is infectious and functions as a messenger RNA for ORF1a and ORF1b. A frame-shifting mechanism between these two nonstructural polypeptides translates RNA-dependent RNA polymerase. In replication complexes near intracellular membranes, ORF1a and ORF1b are cleaved to generate individual nonstructural proteins that are involved in replication. The resulting subgenomic RNA contains ORF2 and encodes precursor capsid protein (VP90). VP90 is proteolytically cleaved during packaging and produces immature capsids made of VP70. Following encapsidation, immature capsids are released from the cell without lysis. Extracellular virions are cleaved by Trypsin and form mature infectious virions.

Astroviruses are 28-30 nm non-enveloped viruses with T-3 icosahedral symmetry. They have spherical shapes and consist of a capsid protein shell. Astroviruses have distinctive five or six pointed star-like projections on 10% of the virions (the other virions have smooth surfaces). The virion capsid is expressed from a subgenomic mRNA and its precursor undergoes multiple cleavages to make the VP70 protein. Capsids that are made of the VP70 protein are cleaved by trypsin to make particles that are very infectious (VP25/26, VP27/29 and VP34). The spikes that create the star-like appearance on the virion surface are made by two structural proteins (VP25 and VP27) while the capsid shell is made from VP34.

Astroviruses have a genome composed of a single strand of positive sense RNA. The strand has a poly A tail at the 3' end, but no 5' cap but instead is linked to a VPg protein. With the exclusion of polyadenylation at the 3' end, the genome is between 6.8 and 7.9 kb long. The genome is arranged into three open reading frames (ORFs), with an overlap of approximately 70 nucleotides between ORF1a and ORF1b. The remaining ORF is known as ORF2. ORF2 encode the structural proteins, which are -at least- VP26, VP29 and VP32, the most antigenic and immunogenic of these being VP26. This protein is probably involved in the first steps of viral infection, being a key factor in the biological cycle of astroviruses. The human astrovirus genome mutation rate has been estimated to be 3.7×10⁻³ nucleotide substitutions per site per year with the synonymous changes rate of 2.8×10⁻³ nucleotide substitutions per site per year. The capability for genetic recombination appears to be present in type-3 and type-4 human astroviruses, and in porcine astrovirus strains.

Replication of astroviruses occur in the cytoplasm. Astrovirus RNA is infectious and functions as a messenger RNA for ORF1a and ORF1b, with translation initiation thought to be mediated by VPg similar to Caliciviridae. A frame-shifting mechanism between these two nonstructural polypeptides translates RNA-dependent RNA polymerase (RdRp). In replication complexes near intracellular membranes, ORF1a and ORF1b are cleaved to generate individual nonstructural proteins that are involved in replication. RdRp transcribes subgenomic RNA from the subgenomic promoter, which enables higher production of structural proteins. Subgenomic RNA contains ORF2 which encodes precursor capsid protein (VP90). VP90 is proteolytically cleaved during packaging and produces immature capsids made of VP70. Following encapsidation, immature capsids are released from the cell without lysis. Extracellular virions are cleaved by Trypsin and form mature infectious virions.