Beyond the Gastrointestinal Tract: The Emerging and Diverse Tissue Tropisms of Astroviruses

Abstract

Astroviruses are single stranded, positive-sense RNA viruses that have been historically associated with diseases of the gastrointestinal tract of vertebrates, including humans. However, there is now a multitude of evidence demonstrating the capacity of these viruses to cause extraintestinal diseases. The most striking causal relationship is neurological diseases in humans, cattle, pigs, and other mammals, caused by astrovirus infection. Astroviruses have also been associated with disseminated infections, localized disease of the liver or kidneys, and there is increasing evidence suggesting a potential tropism to the respiratory tract. This review will discuss the current understanding of the tissue tropisms for astroviruses and their emerging capacity to cause disease in multiple organ systems.

Keywords: astroviruses; encephalitis; gastroenteritis; hepatitis; respiratory disease; tropism.

Figure 1

Timeline of the organ systems associated with astrovirus disease. The originally identified astrovirus strain and disease association are shown. Currently, there is a hypothesized link between astrovirus infection and respiratory disease, but no experimental data exists supporting this association.

Figure 2

Phylogenetic relationships of representative astrovirus ORF2 sequences. A total of 53 astrovirus genomes were selected for analysis and include the 22 astrovirus species recognized by ICTV, genotypes implicated in extraintestinal diseases, and recently identified representative reptilian, amphibian, fish, invertebrate, and plant astrovirus-like genomes (see Supplementary Materials for full list). Astrovirus amino acid sequences for ORF2 were aligned using MUSCLE and noninformative alignments removed by TrimAI [10,11]. A maximum likelihood tree was generated in MEGA X, using the LG model with frequencies and discrete gamma distribution [12]. A total of 100 bootstraps were completed with bootstrap values >50 represented on the tree. Astrovirus clades that have been implicated in extraintestinal diseases are highlighted in red. MAstV: mamastrovirus; AAstV: avastrovirus; HAstV: human astrovirus; AstV: astrovirus.