The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses

“without causing disease [12] (Figures 1 and 2).”

“Bat astroviruses were first detected in 2008 in Hong Kong [77] and subsequently detected in bats in China [78,79], North America [80], Germany [81], Hungary [82], and the Czech Republic [83] from numerous bat species, with detection rates ranging from 36% to 100% in Miniopterus magnater bats and from 50% to 70% of Min…”

“VA1/HMO-C viruses have been detected and associated with encephalitis in immunocompromized children and adults [11,40,47] and acute respiratory disease [48].”

“Bat astroviruses were first detected in 2008 in Hong Kong [77] and subsequently detected in bats in China [78,79], North America [80], Germany [81], Hungary [82], and the Czech Republic [83] from numerous bat species, with detection rates ranging from 36% to 100% in Miniopterus magnater bats and from 50% to 70% of Min…”

“The viruses lack a RNA-helicase domain encoded within the genome and utilize a ribosomal frameshifting mechanism to translate the RdRp, which distinguishes the Astroviridae family from other non-enveloped ssRNA virus families such as Picornaviridae and Caliciviridae [20,21].”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14–16,67–69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in China [71].”

“Whilst primarily associated with asymptomatic or diarrheal disease in humans, there are several reports of central nervous system (CNS) complications such as acute flaccid paralysis [9], meningitis, and encephalitis [10,11].”

“One of the mammalian species with the highest burden of symptomatic astrovirus infection is mink; infection is associated with pre-weaning diarrhea syndrome and the neurological condition “shaking mink syndrome” [17,76].”

“Bat astroviruses were first detected in 2008 in Hong Kong [77] and subsequently detected in bats in China [78,79], North America [80], Germany [81], Hungary [82], and the Czech Republic [83] from numerous bat species, with detection rates ranging from 36% to 100% in Miniopterus magnater bats and from 50% to 70% of Min…”

“A study in the USA revealed the high level of co-infections in pigs (13.9%), revealing the frequent opportunity for recombination, especially between viruses of different lineages [61].”

“Following an incubation period of 3–4 days, symptoms including diarrhea, vomiting, abdominal pain, and fever are often reported [7,8].”

“VA1/HMO-C viruses have been detected and associated with encephalitis in immunocompromized children and adults [11,40,47] and acute respiratory disease [48].”

“MLB2 viruses were first identified in Vellore, India [42] with the majority of strains subsequently identified in Japan, The Gambia, and Switzerland with limited detection in Turkey, USA, Kenya, China, and Thailand and prevalence reported in the range of 0.3% to 1.5% [40] .”

“The first serotype of ANV (ANV-1) was isolated from a healthy broiler chick in 1976 [99] and was initially regarded as a picornavirus, subsequently reclassified within the Astroviridae family in 2000 [100].”

“In animals, astrovirus infection may be asymptomatic or associated with enteric disease and a range of other symptoms indicative of the involvement of other organ systems including hepatitis and nephritis in avian species [12, 13] , and neurological symptoms in cattle [14] [15] [16] and mink [17] .”

“The first "non-classic" HAstV strain characterized was MLB1, the virus was detected in a stool sample from a 3 year old Australian child with acute diarrhea in 1999; the child had previously received a liver transplant [39] .”

“Subsequent molecular characterization based on viral reactivity to polyclonal antibodies and nucleotide sequence analysis led to the recognition of eight serotypes (HAstV-1–8), now termed “classic” HAstV [18,33,34].”

“Viruses from the Mamastrovirus genus have also been characterized from marine mammals including stellar sea lion (SslAstV) and California sea lions (CslAstV), minke whale, orca whale, and bottlenose dolphins (BdAstV) (Figure 1a,b) [26].”

“Chicken astrovirus has been associated with runting-stunting syndrome (RSS) in chickens characterized by poor weight gain, lower feed conversion, and mortality resulting in economic losses [97], and “white chicks” disease associated with increased mortality of embryos and chicks, weakness, and white plumage [98].”

“TAstV-2 was identified in 1996 [94], and is likely to be classified within the species Avastrovirus 3 and is primarily associated with PEMS [95].”

“CNS complications associated with astrovirus infection have been reported in recent years, including acute flaccid paralysis, with some fatalities reported in children with underlying immune disorders [30,31].”

“Astrovirus infection in ducks has been associated with a highly contagious and fatal hepatitis, historically known as duck hepatitis virus type 2 (DHV-2), which was described in the U.K. and subsequently serotype DHV-3 was isolated in the USA [5, 84, 105, 106] .”

“Astroviruses were first described from human infants with diarrhea and were subsequently identified in the young of numerous mammalian and avian species [4,5].”

“In animals, astrovirus infection may be asymptomatic or associated with enteric disease and a range of other symptoms indicative of the involvement of other organ systems including hepatitis and nephritis in avian species [12,13], and neurological symptoms in cattle [14–16] and mink [17].”

“9%), revealing the frequent opportunity for recombination, especially between viruses of different lineages [61].”

“Porcupine strains isolated in China also cluster with unclassified PAstV-2 strains suggesting further interspecies transmission of these viruses (Figure 1a) [64].”

“A study in the USA revealed the high level of co-infections in pigs (13.9%), revealing the frequent opportunity for recombination, especially between viruses of different lineages [61].”

“In animals, astrovirus infection may be asymptomatic or associated with enteric disease and a range of other symptoms indicative of the involvement of other organ systems including hepatitis and nephritis in avian species [12, 13] , and neurological symptoms in cattle [14] [15] [16] and mink [17] .”

“Subsequently there have been sporadic reports of astrovirus outbreaks in turkeys, associated with enteritis and growth depression [93].”

“A study in the USA revealed the high level of co-infections in pigs (13.9%), revealing the frequent opportunity for recombination, especially between viruses of different lineages [61].”

“Avian astrovirus have been detected in outbreaks of enteric disease in turkey poults, and avian astrovirus were first reported as an agent of gastroenteritis and mortality in young turkeys in 1980, associated with a condition known as poult enteritis mortality syndrome (PEMS) [91,92].”

“The greatest diversity in the genome is within the ORF2 region, which is characterized by a highly-conserved N-terminal domain (amino acids (aa) 1–424), a hypervariable domain (aa 425–688) which is believed to form the capsid spike and contribute to receptor binding, and a highly acidic C-terminal domain [22,23].”

“A recombinant strain derived from porcine astrovirus and human HAstV-3 strains was reported from piglets and children from various regions of Colombia [62].”

“Canine strains form a small, discrete cluster comprising species MAstV-5, within a lineage comprised of dolphin and sea lion clades representing species MAstV-4 and -11 [55,56], and feline, porcine, and human strains are more distantly related within the same lineage (Figure 1a).”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14–16,67–69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in China [71].”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14–16,67–69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in China [71].”

“Subsequent molecular characterization based on viral reactivity to polyclonal antibodies and nucleotide sequence analysis led to the recognition of eight serotypes (HAstV-1–8), now termed “classic” HAstV [18,33,34].”

“MLB3 viruses were first detected in India in 2004 [43], with subsequent detection in Kenya and The Gambia and the prevalence in stools ranges from 0.6% to 3.1% [40,44].”

“The first serotype of ANV (ANV-1) was isolated from a healthy broiler chick in 1976 [99] and was initially regarded as a picornavirus, subsequently reclassified within the Astroviridae family in 2000 [100].”

“The prevalence of VA1/HMO-C viruses in stools ranges from 0.2% to 1.6% in diarrheic and non-diarrheic subjects worldwide, with limited detection in Nepal, Japan, Tanzania, The Gambia, France, and the U.K. [9,44,47].”

“One of the mammalian species with the highest burden of symptomatic astrovirus infection is mink; infection is associated with pre-weaning diarrhea syndrome and the neurological condition “shaking mink syndrome” [17,76].”

“The viruses lack a RNA-helicase domain encoded within the genome and utilize a ribosomal frameshifting mechanism to translate the RdRp, which distinguishes the Astroviridae family from other non-enveloped ssRNA virus families such as Picornaviridae and Caliciviridae [20,21].”

“Astroviruses have been detected in the environment and the durability of the virus in this environment may greatly contribute to cross-species transmission within and between terrestrial and aquatic species, generating significant diversity [115].”

“L-bat species), and numerous other strains awaiting classification, some of which are considered as tentative new species (designated by a ∧ symbol in the phylogenetic trees) (Figure 1a) [27,28].”

“A study in the USA revealed the high level of co-infections in pigs (13.9%), revealing the frequent opportunity for recombination, especially between viruses of different lineages [61].”

“In animals, astrovirus infection may be asymptomatic or associated with enteric disease and a range of other symptoms indicative of the involvement of other organ systems including hepatitis and nephritis in avian species [12, 13] , and neurological symptoms in cattle [14] [15] [16] and mink [17] .”

“The important role that ecotones play in astrovirus cross-species transmission has been proposed [112].”

“Following an incubation period of 3–4 days, symptoms including diarrhea, vomiting, abdominal pain, and fever are often reported [7,8].”

“Based on evolutionary analysis, an interspecies transmission pathway has been hypothesised whereby porcine strains may have been transmitted to cats and subsequently to humans, possibly involving other intermediary species suggesting sustained interspecies transmission events [53].”

“The greatest diversity in the genome is within the ORF2 region, which is characterized by a highly-conserved N-terminal domain (amino acids (aa) 1–424), a hypervariable domain (aa 425–688) which is believed to form the capsid spike and contribute to receptor binding, and a highly acidic C-terminal domain [22,23].”

“Astrovirus infection in ducks has been associated with a highly contagious and fatal hepatitis, historically known as duck hepatitis virus type 2 (DHV-2), which was described in the U.K. and subsequently serotype DHV-3 was isolated in the USA [5, 84, 105, 106] .”

“Fewer land dwelling wild birds have been found to harbor avian astroviruses including doves and pigeons (order Colombiformes), European roller (order Coraciiformes), and black-naped monarch (order Passeriformes) [51,104,110,111].”

“Astroviruses have been detected in numerous wild aquatic species including teals, pintails, and shovelers (belonging to the order Anseriformes), sanderlings (order Charadriiformes), and herons and spoonbills (order Pelecaniformes) [86,109].”

“Characterization of an outbreak of diarrhea in a group of captive cheetahs in a breeding facility identified an astrovirus strain most closely related to feline strains (Figure 1a), however it is not clear if this is a recent transmission from domesticated cats or if the virus is circulating independently in cheetahs…”

“A virus with a recombination event within the ORF1a region has been identified [119].”

“A third serotype (ANV-3) detected in chickens and turkeys with RSS and locomotion impairment has been proposed based on sequencing of the ORF1a region, however complete genome sequences are unavailable for adequate comparisons to the recognized serotypes [102].”

“Farms and abattoirs have also been recognized as environments facilitating transmission between livestock species and to farm and abattoir workers [114].”

“Human astroviurses (HAstVs) have been recognized as one of the major causes of acute gastroenteritis in children, associated with 2–8% of infections [6].”

“Astroviruses infecting guineafowl are closely related to TAstV-2 strains based on analysis of the RdRp region [96], however the capsid region is distinct to TAstV-2 strains, forming a discrete cluster in a lineage of unassigned viruses suggesting they are closely related to CAstV-B strains (Figure 2a).”

“Astrovirus infection in humans has been primarily associated with diarrhea and vomiting, accounting for up to 10% of sporadic gastroenteritis cases in some regions [29].”

“Astroviruses are named due to the distinct five-pointed or six-pointed star-like appearance of some virions when visualized under an electron microscope (EM); astrovirus is derived from the Greek word astron meaning star [1] [2] [3] .”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14] [15] [16] [67] [68] [69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in Ch…”

“In addition to AAstV-1 comprised of TAstV-1, AAstV-2 comprised of ANV1 and ANV2, and AAstV-3 comprised of TAstV-2 and duck astrovirus 1 (DAstV-1), there are numerous yet-to-be classified viruses, including Turkey astrovirus 3 (TAstV-3), chicken astrovirus A (CAstV-A), chicken astrovirus B (CAstV-B) [88,89], GFAstV, an…”

“Phylogenetic analysis also reveals that bovine-like astrovirus strains have been isolated from numerous wild species including water buffalo, yak, and European roe deer (CcAstV-1 and CcAstV-2) suffering from gastroenteritis [73].”

“Two serotypes were previously recognized, BoAstV-1 and BoAstV-2 [72], however based on phylogenetic analysis there are multiple lineages of BoAstV strains circulating in farmed bovine populations, and the close clustering of bovine, porcine, and ovine strains in multiple lineages reflects the common interspecies trans…”

“Canine strains form a small, discrete cluster comprising species MAstV-5, within a lineage comprised of dolphin and sea lion clades representing species MAstV-4 and -11 [55,56], and feline, porcine, and human strains are more distantly related within the same lineage (Figure 1a).”

“Full-and partial-genome sequence analysis has identified multiple strains that have undergone recombination events, which are predominately located within the ORF1b/ORF2 junction region of the genome, which is a region with an RNA secondary structure predicted to contain a stable hairpin structure [21, 34, [116] [117]…”

“Astrovirus infection has been implicated in pre-hatching mortality in ducklings and goslings [87] .”

“Chicken astrovirus has been associated with runting-stunting syndrome (RSS) in chickens characterized by poor weight gain, lower feed conversion, and mortality resulting in economic losses [97] , and "white chicks" disease associated with increased mortality of embryos and chicks, weakness, and white plumage [98] .”

“Wild boars showing no symptoms of enteric disease, housed in a captive breeding park with no contact with domesticated pigs, were found to harbor astrovirus strains with a high degree of genetic similarity to porcine strains comprising MAstV-26 and suggests that the virus may be derived from commonly circulating porci…”

“VA4 has only been detected in Nepal [43] and the BF34 strain has only detected in Burkina Faso [45].”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14–16,67–69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in China [71].”

“The prevalence of VA2/HMO-A viruses in stools ranges from 0.3% to 2.3%, with strains also detected in Egypt, Japan, USA, Kenya, and China [40].”

“Full-and partial-genome sequence analysis has identified multiple strains that have undergone recombination events, which are predominately located within the ORF1b/ORF2 junction region of the genome, which is a region with an RNA secondary structure predicted to contain a stable hairpin structure [21, 34, [116] [117]…”

“However, a seroepidemiologic study in the USA revealed that primary exposure to MLB1 occurs in childhood and that seropositivity reached 100% by adulthood suggesting the widespread circulation of the virus in the human population [41].”

“A large diverse lineage, largely comprised of unclassified viruses or tentatively classified viruses awaiting approval encompasses divergent marmot and rabbit strains (MAstV-23), small, discrete clusters of porcine/ovine/bovine strains (MAstV-24), divergent rat strains (MAstV-25), and unclassified mouse and mink strai…”

“Porcupine strains isolated in China also cluster with unclassified PAstV-2 strains suggesting further interspecies transmission of these viruses (Figure 1a) [64].”

“Adopting a nomenclature that records the appropriate metadata associated with sample collection including host, location, date of collection, and determined species and serotype as proposed by Martella and colleagues would vastly improve the usability of strains for more complex analyses [38].”

“In addition to AAstV-1 comprised of TAstV-1, AAstV-2 comprised of ANV1 and ANV2, and AAstV-3 comprised of TAstV-2 and duck astrovirus 1 (DAstV-1), there are numerous yet-to-be classified viruses, including Turkey astrovirus 3 (TAstV-3), chicken astrovirus A (CAstV-A), chicken astrovirus B (CAstV-B) [88,89], GFAstV, an…”

“In addition to AAstV-1 comprised of TAstV-1, AAstV-2 comprised of ANV1 and ANV2, and AAstV-3 comprised of TAstV-2 and duck astrovirus 1 (DAstV-1), there are numerous yet-to-be classified viruses, including Turkey astrovirus 3 (TAstV-3), chicken astrovirus A (CAstV-A), chicken astrovirus B (CAstV-B) [88,89], GFAstV, an…”

“Full-and partial-genome sequence analysis has identified multiple strains that have undergone recombination events, which are predominately located within the ORF1b/ORF2 junction region of the genome, which is a region with an RNA secondary structure predicted to contain a stable hairpin structure [21, 34, [116] [117]…”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14–16,67–69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in China [71].”

“A highly divergent group of mink strains detected in China represent a novel clade of astroviruses that were distantly related to previously described mink astrovirus and were closely related to chicken and turkey astroviruses (Figure 2a,b) [113].”

“HAstV-4 and HAstV-8 have been associated with infection of older children and longer duration of diarrhea (>7 days) [36,37].”

“Avian astrovirus have been detected in outbreaks of enteric disease in turkey poults, and avian astrovirus were first reported as an agent of gastroenteritis and mortality in young turkeys in 1980, associated with a condition known as poult enteritis mortality syndrome (PEMS) [91,92].”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14–16,67–69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in China [71].”

“Numerous human recombinant strains have been reported between HAstV strains, including strains with HAstV-1 (ORF1b) and HAstV-4 (ORF2) parental viruses, HAstV-1 (ORF1b) and HAstV-3 (ORF2) parental viruses, HAstV-3 (ORF1b) and HAstV-2 (ORF2), and VA2 (ORF1b) and MLB1 (ORF2) parental viruses [116, [119] [120] [121] .”

“The first bovine astrovirus was detected in England in 1978 [66] and bovine astrovirus strains have been detection in association with neurological disease, including encephalitis (BoAstV-CH13/NeuroS1) [14–16,67–69] and diarrheal disease in calves in South Korea [70] and cattle and buffalo calves in China [71].”

“Astroviruses have been detected in numerous wild aquatic species including teals, pintails, and shovelers (belonging to the order Anseriformes), sanderlings (order Charadriiformes), and herons and spoonbills (order Pelecaniformes) [86,109].”

“The highly divergent strains isolated from European roller (Er/SZAL6/HUN/2011 and Er/BMTK529/HUN/2011) exhibited low identity to avian and mammalian astroviruses, cluster within the MAstV lineage, and were likely derived from multiple recombination and interspecies transmission events [51].”

“L-bat species), and numerous other strains awaiting classification, some of which are considered as tentative new species (designated by a ∧ symbol in the phylogenetic trees) (Figure 1a) [27,28].”

“This virus remains to be classified by the ICVT, however the capsid regions clusters closest to the MLB1-3 viruses suggesting an evolutionary relationship to these divergent human astroviruses [50] (Figure 1a ).”

“Duck astrovirus DAstV-3/CPH has been suggested to transmit horizontally and vertically [108] and DAstV-3/CPH viruses have also been detected in goslings [107].”

“A further ORF, termed ORFX, has been observed in classic HAstVs and some mammalian astroviurses, overlapping the 5 end of ORF2 which may be translated through a leaking scanning mechanism [19] .”

“In addition to AAstV-1 comprised of TAstV-1, AAstV-2 comprised of ANV1 and ANV2, and AAstV-3 comprised of TAstV-2 and duck astrovirus 1 (DAstV-1), there are numerous yet-to-be classified viruses, including Turkey astrovirus 3 (TAstV-3), chicken astrovirus A (CAstV-A), chicken astrovirus B (CAstV-B) [88,89], GFAstV, an…”

“Fewer land dwelling wild birds have been found to harbor avian astroviruses including doves and pigeons (order Colombiformes), European roller (order Coraciiformes), and black-naped monarch (order Passeriformes) [51,104,110,111].”

“The second serotype (ANV-2) was later described from chicks with stunted growth [101].”

“CNS complications associated with astrovirus infection have been reported in recent years, including acute flaccid paralysis, with some fatalities reported in children with underlying immune disorders [30,31].”

“This diversity likely reflects the varying origins of these viruses, in particular highlighting frequent interspecies transmission and recombination events [58] [59] [60] .”

“The classification of the Astrovirus genus within the family Astroviridae was recognized by the International Committee for Taxonomy of Viruses (ICTV) in 1995 and the classification scheme has been modified numerous times over the intervening years [24].”

“This diversity likely reflects the varying origins of these viruses, in particular highlighting frequent interspecies transmission and recombination events [58] [59] [60] .”

“Fewer land dwelling wild birds have been found to harbor avian astroviruses including doves and pigeons (order Colombiformes), European roller (order Coraciiformes), and black-naped monarch (order Passeriformes) [51, 104, 110, 111] .”

“Bat astroviruses were first detected in 2008 in Hong Kong [77] and subsequently detected in bats in China [78,79], North America [80], Germany [81], Hungary [82], and the Czech Republic [83] from numerous bat species, with detection rates ranging from 36% to 100% in Miniopterus magnater bats and from 50% to 70% of Min…”

“, 2008) and sequence based phylogenetics, astroviruses have been classified by their ORF2 full length amino acid sequence into three species of AAstV and 19 species of MAstV (Bosch et al., 2012; Donato and Vijaykrishna, 2017; Krishnan, 2014).”

“AstVs have been detected in humans and a variety of animal species, including nonhuman primates, other mammals and avian species [3] [4] [5] .”

“Genera Mamastrovirus (MAstV) and Avastrovirus (AAstV) make up the family Astroviridae (Appleton, 1975; De Benedictis et al., 2011; Donato and Vijaykrishna, 2017).”