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.

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2

“…Compared to VA1-s2m-WT, VA1-s2m 12, 18, 24, 33 was lower at 48 and 96 hpi (48 hpi P= 0.045, 96 hpi P= 0.0014). VA1-s2m 9 and VA1-s2m 12, 33 had lower RNA at 96 hpi compared to WT (VA1-s2m 9 : P< 0.001, VA1-s2m 12, 33 P= 0.049), while VA1-s2m 18, 24 had no difference (P> 0.06). ( C ) Multi-step growth curve of virus titers with a significant difference between WT and mutants identified by two-way ANOVA (F[4,40]= 11.4, P< 0.001).…”

“…1B) , but has been identified to form potential long-distance tertiary interactions with nucleotide 30 in the SARS-CoV-1 s2m crystal structure 4 . To evaluate the significance of this position and nucleotide residue, we mutated position 9 in the VA1 s2m by replacing the adenine for a cytosine (VA1-s2m 9 ; Table S1 ). The VA1-s2m 9 mutant could be propagated in 8 out of 9 replicates ( Table 1 ).…”

“…To evaluate the significance of this position and nucleotide residue, we mutated position 9 in the VA1 s2m by replacing the adenine for a cytosine (VA1-s2m 9 ; Table S1 ). The VA1-s2m 9 mutant could be propagated in 8 out of 9 replicates ( Table 1 ).…”

“…We also identified that nucleotide positions that are not predicted to form G-C base pairs can be modified in the s2m (VA1-s2m 9 ), but this resulted in reduced production of viral progeny (Fig. 2C).…”

High Seropositivity Rate of Neutralizing Antibodies to Astrovirus VA1 in Human Populations

“…In addition, astroviruses are an emerging cause of fatal central nervous system (CNS) infections in humans and other mammals ( 6 ). Astroviruses may have additional extraintestinal tropisms, including the capacity to infect the liver and respiratory tract and to cause systemic disease ( 7 ). Currently, there are four species of astroviruses that are known to frequently infect humans, mamastrovirus 1 (classic human astrovirus 1-8), mamastrovirus 6 (astrovirus MLB1-MLB3), mamastrovirus 8 (astrovirus VA2/HMO-A and VA4), and mamastrovirus 9 (astrovirus VA1/HMO-C [VA1], VA3/HMO-B, and BF34/VA5) ( 1 , 8 – 17 ).…”