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Human : A Brief Review Pam & Omote

HUMAN ASTROVIRUSES: A BRIEF REVIEW

Martin Zang Pam1 & Victor Omote2 1. Department of Animal Health, Federal College of Animal Health and Production Technology, Vom, Nigeria ([email protected]) 2. Department of Laboratory Services, Central Hospital Warri, Nigeria ([email protected])

Abstract Astroviruses belonging to the family Astroviridae are cosmopolitan and infect a wide range of mammalian and avian hosts. Human Astroviruses (classic HAstV) under the genera within eight (8) different serogroups are responsible for 2-9% of all acute nonbacterial in children worldwide. Although its pathogenicity and pathogenesis are still poorly understood, attachment of the viral spike and protein to intestinal epithelial cells activates a process which results in mal-absorption, loss of secretory functions, and reduced permeability. The possibility for cross-species has raised alarm about possible zoonotic transmission. Thus, its , epidemiology, pathology, immunology, diagnosis and management are briefly reviewed. Keywords: Human Astroviruses, epidemiology, pathology, immunology, diagnosis, management, interspecies transmission, zoonosis ______Introduction nonstructural proteins (nsPs) involved in RNA Astroviruses (AstVs) are a diverse family of and replication, while ORF2 that infect a wide range of mammalian encodes the structural proteins, which are and avian hosts. Named after their distinct expressed from a subgenomic RNA (Monroe five-pointed or six-pointed star-like et al., 1993). The HAstV replication cycle appearance when visualized under an Electron shares many common features with the microscope (EM); is derived from replication cycle of members of the the Greek word astron meaning “star” (Risco family. After cell entry and et al., 1995). Although there were some uncoating, the two main nonstructural undocumented reports about earlier outbreaks polyproteins are translated from the VPg- in China, the first reported cases of Human linked genomic RNA. Cleavage of these Astrovirus associated outbreak was recorded polyproteins results in the individual in 1975 following the identification of the star- nonstructural proteins required for like virion particles in the stool and vomitus of replication, which takes place in replication children from a maternity ward (Appleton and complexes assembled in close association with Higgins, 1975). Belonging to the family intracellular membranes. This process results Astroviridae, astroviruses are small, positive- in the formation of both genomic and sense, single stranded, and non-enveloped subgenomic , which are produced in RNA viruses measuring ~28 to 35 nm in large quantities to ensure the production of length and enclosed in a nucleocapsid coat high yields of structural proteins. After (D’Souza, 2015). The genome contains three encapsulation and maturation, virions are open reading frames (ORFs), named from the released from the cell (Marczinke et al., 1994). 5′ end to the 3′ end ORF1a, ORF1b, and HAstV is cosmopolitan and is ORF2. ORF1a and ORF1b encode the believed to be responsible for 5–9% of the www.ijsar.org.ng INTERNATIONAL JOURNAL OF SCIENCE AND APPLIED RESEARCH, VOL. 4, Nos.1&2 2021 ISSN 2504-9070 79

Human Astroviruses: A Brief Review Pam & Omote

cases of gastroenteritis in young children is believed to play a role in the (Monroe et al., 2001). Humans of all ages are initiation and severity of HAstV infection. susceptible to astrovirus infection. However, Human studies among healthy volunteers children, the elderly, and those that are revealed individuals with circulating immunocompromised are more susceptible. against the were either Viral transmission peak seems to be season asymptomatic or displayed mild symptoms dependent. In temperate regions, transmission when compared to those without circulating peak occurs during the winter months while antibodies (Midthun et al., 1993). Cell culture the raining season accounts for bulk of propagation of some classic HAstVs is transmission for tropical regions (Glass et al., possible with the aid of trypsin (Willcocks et 1996; Abad et al., 2001). Fecal-oral route al., 1994) but electron microscopy and account for bulk of HAstV transmission with immunological assays are the commonly used few cases of zoonotic transmission reported diagnostic methodology before the advent of (Meliopoulos et al., 2014). Although disease molecular detection techniques. The usage of formation process (pathogenesis) is still poorly these techniques is dependent on availability understood, it is believed that attachment of of equipment, skilled-man power, number of viral particle via its spikes to epithelial cells of samples to assay, and purpose of analysis the intestine produces a complex that disrupts (diagnosis or research). HAstV are normal epithelial cells functionality and results usually self-limiting and resolves within 2-6 in mal-absorption, loss of secretory functions, days. However, serious gastroenteritis may and reduced permeability (Nighot et al., 2010; require oral or intravenous fluid replacement Meliopoulos et al., 2016). Unlike other to avoid . There are reports gastrointestinal viruses, the virulence factors proposing the use of probiotics, flavonoids and of astroviruses remain poorly understood. intravenous treatment with IgG for immune- However, studies on avian model have compromised hosts with severe or persistent implicated the capsid protein to serve as an (Britton and Versalovic 2008; Superti responsible for the associated et al., 1990; Björkholm et al., 1995). diarrhoea (Meliopoulos et al., 2016). Data Prevention and control strategies employed emanating from studies on human viruses against HAstV may be transmission route have demonstrated that the capsid protein of or/and host targeted. Since most transmission HAstV acts as an inhibitor of the complement occurs via the fecal-oral route, improved system, which constitutes an important innate , proper fruits and response against bacterial and viral infections handling as as adequate of (Bosch et al., 2014). HAstV infections are seafood are measures proposed to target the usually asymptomatic with few symptomatic transmission route. Host dependent control cases among immune-compromised strategies revolve around prompt diagnosis individuals. However, symptomatic cases are and management pending the availability of usually characterized by a mild, watery commercial . With the eminent threat diarrhoea that lasts 2 to 3 days, associated with posed by zoonotic diseases and the possibility , , anorexia, and . of zoonotic transmission of Astroviruses, this Few cases of systemic invasion resulting in review presents existing knowledge, highlights disseminated lethal infections among highly recent findings and escalates research immune-compromised children have also been gaps/limitations. reported (Wunderli et al., 2011). Although the Historical perspective mechanism is still poorly understood, adaptive

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Human Astroviruses: A Brief Review Pam & Omote

Although there were some undocumented implicated Astroviruses to be a leading cause reports about earlier outbreaks of human of gastroenteritis among children and immune- Astrovirus infection in China, it was in 1975 compromised adults by the year 1998. From that Appleton and Higgins reported the early 2000 till date, lots of metagenomic presence of a 28 to 30nm particle in stools of surveillance studies have led to the children vomiting and suffering from mild identification of a new serotype bringing the diarrhea in a maternity ward (Appleton and number of classic Human Astroviruses to Higgins 1975). That same year, Madeley and eight serotypes and another two groups of Cosgrove described a distinct five-pointed or novel Astroviruses referred to as the Non- six-pointed star-like particle under an electron classic which are commonly referred to as microscope when they viewed stool samples HAstV-MLB and HAstV-VA/HMO from infants suffering from diarrhea and (Finkbeiner et al., 2008; Finkbeiner et al., named it Astro meaning “star-like” (Risco et 2008; Finkbeiner et al., 2009) al., 1995) In 1981, Lee and Kurtz were able to Taxonomy and classification propagate Astroviruses in cell culture (primary Viruses belonging to the Astroviridae family human embryonic kidney cells) This giant were initially grouped into one genus stride resulted in the differentiation of (Astrovirus) based on their morphology Astroviruses from other agents, such as the (Bosch et al., 2014). This classification was Norwalk agent, which cannot be grown in adopted by the International Committee for culture. The same pair of researchers Taxonomy of Viruses (ICTV) in 1995, but has identified five serotypes of Astrovirus in 1984 undergone several modifications over the using antisera (Kurtz and Lee 1984). In 1988, years (Krishnan, 2004). In 2004, two genera Hermann and co-workers developed Mamastrovirus (MAstV) and monoclonal antibodies against Human (AAstV) were created from the Astrovirus Astroviruses which resulted in their diagnosis genus based on origin of host. Astroviruses using enzyme immune-assay. The production with mammalian host were grouped under the of monoclonal antibodies paved the way for genus “Mamastrovirus” while astroviruses that several modifications that resulted in the infects avian species were categorized into the identification of two extra serotypes bringing Avastrovirus genus (Donato and Vijaykrishna, the total to seven serotypes in 1991. The first 2017). Taxonomy of Astroviruses from the complete Human Astrovirus genome sequence to Genera level is summarized below; occurred in 1994. Improved knowledge of its Realm genomic and subgenomic organization in Kingdom combination with findings from the processing Phylum of its polyprotein resulted in the clamour for a Class Stelpaviricetes re-classification of the Astroviruses and their Order Stellavirales separation from the families Picornaviridae Family Astroviridae and Caliciviridae which was eventually Genera Avastrovirus and Mamastrovirus adapted by the International Committee for the Taxonomy of Viruses (ICTV) in 1995 The advent of genome sequencing and (Monroe et al.,1995). The classification of extensive epidemiological studies has theses viral particles into their own family rendered the species-based classification (Astroviridae) and subsequent modification in inadequate. Interspecies transmission of technologies used for their diagnosis led to viruses and diversity of viruses within one increased epidemiological studies which host prompted the ICTV in 2010 to propose

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the classification of astroviruses based on the located at the ends of the AstV genome amino acid sequence of the ORF2 genome (Bosch et al., 2014). No Internal ribosome region, recommending that different strains of entry site (IRES) has so far been described in the same astrovirus species should share >75% AstV (a feature it shares with viruses grouped identity in the capsid proteins (Bosch et in Caliciviridae family but not with other al.,2012). positive sense single-stranded RNA viruses Astroviruses of the same genotypes are further (Racaniello V, 2007; Lindenbach and Rice classified into different serotypes based on 2007; Green 2007). In addition to the poly (A) their antigenicity. While all eight classic tail consisting of around 30 , a highly HAstVs clearly correspond to different conserved secondary element is present at the serotypes, non-classic Astroviruses still 3′ end of the AstV genome. This secondary requires series of investigation to determine structure is also present in the genome of some their antigenic variations (Bosch et al., 2014). members of , , and Structure and Genome but its function is yet to be Human Astroviruses (HAstV) are single determined (Robertson et al., 2005; Jonassen stranded, positive-sense, non-enveloped RNA et al., 1998). viruses of icosahedral particle symmetry that The lengths of ORF1a, ORF1b, and ORF2 cause a variety of clinical diseases ranging vary depending on the AstV strain. This from diarrhea to , or asymptomatic variation is largely dependent on the insertions infection in children, the elderly and immune- and deletions present at the 3′ end of ORF1a compromised individuals (Bosch et al., 2014). (Guix et al., 2005). ORF1a encodes a putative Measuring 38-41nm, all 8 serotypes consists helicase domain (HEL), several of three capsid proteins and possesses a transmembrane (TM) and coiled-coil (CC) distinctive star-like appearance when observed domains, the protease domain (PRO), a VPg, a under an (Risco et al., hypervariable region (HVR), a nuclear 1995). Surface projections are small and localization signal (NLS), and a putative death surface appears rough with spikes protruding domain (DD). ORF1b encodes the RNA from the 30 vertices (Bosch et al., 2014). With dependent-RNA polymerase (RdRp). ORF2 a buoyant density ranging from 1.35 and 1.37 contains the region coding for the shell g/ml in CsCl, their capsid precursor protein proteins, a P1 domain of unknown function, a (180 copies per particle) is primarily involved variable region containing the P2 domain in viral maturation. which includes the spike proteins, and an AstV genome is a positive-sense ssRNA additional acidic domain at the C terminus molecule of around 6.8 (6.2 to 7.8) kb (Bosch et al., 2014). containing three open reading frames (ORFs), Replication cycle named from the 5′ end to the 3′ end ORF1a, The HAstV replication cycle shares many ORF1b, and ORF2. ORF1a and ORF1b common features with the replication cycle of encode the nonstructural proteins (nsPs) members of the Caliciviridae family (Bosch et involved in RNA transcription and replication, al., 2014). Below is a step by step presentation while ORF2 encodes the structural proteins, of events of the replication cycle of Human which are expressed from a subgenomic RNA Astroviruses as described by Schultz-Cherry (Willcocks and Carter, 1993). Regarding (2013). genome organization, two untranslated regions Attachement to host receptors probably results (UTR’s), the 5′ UTR and the 3′ UTR, of 11 to in clathrin-dependent of the virus 85 and 80 to 85 bases, respectively, are into the host cell.

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Entrance of the virus into the cell causes A full-length negative-sense genomic RNA is reduction in pH which leads to uncoating, and synthesized and used as a template for the release of the viral genomic RNA into the production of both positive-sense genomic cytoplasm. RNA and positive-sense subgenomic RNA. The genome is then translated, giving rise to Subgenomic RNA translation gives rise to the nsP1a1b and nsP1a polyproteins, which are capsid protein precursor VP90. then cleaved by the viral serine protease (in VP90 polyprotein initially assembles into nsP1a) as well as some cellular proteases, immature virions in association with resulting in the individual nonstructural intracellular membranes through its C protein. terminus. Several cellular caspases further Proteolytic processing of polyproteins cleave these VP90 polyproteins close to their nsP1a1b (around 160 kDa) produces the nsP1b C termini once they have dissociated from protein (RdRp) (around 57 kDa) and the nsP1a membranes, resulting in viral protein (around 102 kDa), which is composed of 70-kDa polyproteins (VP70). subsequently cleaved to yield several mature Finally, VP70-containing viral particles would products. be released from cells and proteolytically Replication occurs in viral factories made of processed by trypsin to enhance infectivity. membrane vesicles derived from the ER. Virus release by cell lysis and maturation of the capsid by proteolytic cleavages

Epidemiology nonbacterial diarrhea in children (De HAstVs are distributed all over the world and Benedictis et al., 2011). The mean incidence are associated with 2 to 9% of cases of acute, worldwide is 11%, with 7% and 23% www.ijsar.org.ng INTERNATIONAL JOURNAL OF SCIENCE AND APPLIED RESEARCH, VOL. 4, Nos.1&2 2021 ISSN 2504-9070 83

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incidences in urban and rural areas, disinfecting practices as well as inadequate respectively (Bosch et al., 2013). HAstV hygiene particularly in high-risk settings such incidence is usually higher in developing as hospitals, institutions for the elderly, day countries, although paradoxically, a low care centers, or restaurants, accounts for most incidence of infection is observed in sub- Human Astrovirus cases after Fecal-oral Saharan Africa (Kiulia et al., 2007). transmission. Known as the second most common virus Although astroviruses were initially found in children with diarrhea, Human considered to be so species specific that it led Astroviral infection is prevalent among to their classification based on the host pediatric population (Shastri et al., 1998), but species, concern about the potential zoonotic the elderly and immunocompromised are also transmission of astroviruses to humans has susceptible (Björkholm et al., 1995). Although recently arisen. In comparison to individuals less common among the healthy population, who had no contact with turkey, turkey the typical age range for Human Astrovirus abattoir workers were three times more likely infection is from 0-5years of age, with up to to test positive for antibodies against turkey 90% of children age five years have astroviruses (Meliopoulos et al., 2014). circulating antibodies specific for Astroviruses Pathogenicity and pathogenesis (Mustafa et al., 2000). The lack of suitable cell culture systems for The classic HAstV distribution follows a the majority of the genotypes, coupled with seasonal pattern with a higher incidence of the absence of adequate animal model to study infection in temperate regions in the cold- the disease progression of Astroviruses has weather period and rainy season for tropical hamper complete understanding of its regions (Steele et al., 1998). The cold pathogenesis. However, studies from turkey temperature favours the stability of the virus, model have implicated the viral spikes and while rainy season encourages poor hygiene protein capsids as its key virulent factors (Toh practices that embolden the distribution of the et al., 2016; Bogdanoff et al., 2016). While it virus. is been postulated that both the spikes and The primary route of transmission for Human capsid protein functions in the recognition and Astroviruses is fecal-oral. Viruses released binding to a carbohydrate receptor still with feaces finds its way into water bodies unidentified, the capsid protein has been where it contaminates and drinking water reported to act as an entero- as well as (Le Cann et al., 2004). Common function in inactivating host immune susceptible to become contaminated with responses (complement cascade) (Meliopoulos HAstV at the preharvest stage are bivalve et al., 2016). mollusks grown in polluted waters (Le Reports of Astrovirus studies using human Guyader et al., 2000) and fresh produce colon carcinoma cells type 2 (Caco-2) irrigated with contaminated water, such as revealed that binding of viral particle to , green onion, and other greens, as well susceptible cell line results in the disruption of as soft fruits such as raspberries and tight junctions. Tight junctions are highly strawberries (Pintó and Bosch, 2008). These regulated cell–cell associations that help products are usually consumed with little or no maintain cell polarity and prevent the free cooking and hence are susceptible to act as passage of macromolecules and vehicles for human enteric virus transmission. from one side of the Most institutional outbreaks have been linked epithelium to the other (Torres-Flores and to fomites (Cubitt et al., 1999). Poor Arias, 2015). Junctions are multi-protein

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Human Astroviruses: A Brief Review Pam & Omote

domains composed of trans-membrane , HAstV infection has also proteins, such as occludin and claudins, which been identified as a potential risk factor for interact with cytosolic adapter proteins, like intussusception in infected children (Aminu et Zonula occludens (ZO-1). These interactions al., 2009). connect the cell membrane with the actin Host Immune Responses cytoskeleton. Disruptions of the tight junction The observation that AstV infection is age can result in altered ion and/or solute dependent led to the assumption that immune exchange, increasing fluid to the lumen of protection is acquired after an initial infection. secretory functions, and decrease in epithelial However, the specific immune responses permeability in the intestines are hallmarks of activated upon AstV infections are not yet gastroenteritis caused by Astroviruses (Moser completely understood (Bosch et al., 2014). et al., 2007). It is worthy to note that diarrhea There are epidemiological and clinical studies associated with Astroviruses had little or that have demonstrated that humoral immune nothing to do with epithelial damage or response plays a role in restraining infection inflammation of infected cells (Bosch et al., and disease in humans. Two clinical studies 2014). carried out among human volunteers revealed Clinical manifestation a negative correlation between infection The clinical manifestation of human Astroviral severity and the presence of circulating HAstV infection has been reported to be dependent on antibodies prior to being challenged by the a number of factors (age, immune status, viral particle (Midthun et al., 1993). previous exposure, co-infection with other Molberg and co-workers in 1998 demonstrated entero-viruses and geographical location) the presence of HAstV-specific CD4+ and (Jeong et al., 2012). However, HAstVs, are CD8+ T cells residing in the normal tissue of gastrointestinal pathogens associated with small intestinal biopsy specimens from healthy diarrhea after about 4-5 days of incubation adults in an organ culture system when it was (Lee et al., 2013). Mostly asymptomatic, few challenged with inactivated HAstVs. Thus, it cases are characterized by a mild and watery is clear that both humoral and cell mediated diarrhea, vomiting, fever, anorexia, and adaptive immune responses are involved in abdominal pain (Bosch et al., 2014). Vomiting protecting normal healthy adults from is less prevalent in astrovirus infection than in reinfections. or calicivirus infection. In general, HAstV diarrhea is milder than those caused by Laboratory diagnosis or noroviruses, and it resolves The diagnosis of Astroviruses started with spontaneously, although in some cases HAstV electron microscopy of negatively stained infections have required hospitalization stool samples, but has evolved to more (Bosch et al., 2014). sophisticated molecular methods with Although HAstV are believed to be associated sensitivity and specificity as high as 90-95%. with gastro-intestinal infection, there are The usage of these techniques is dependent on reports of systemic spread resulting to severe availability of equipment, skilled-man power, disseminated lethal infections in highly number of samples to assay, and purpose of immune-compromised children (Wunderli et analysis (diagnosis or research). Each of these al., 2011). Finally, the relationship of HAstV techniques is discussed briefly below. infection to the etiology of intussusception in Electron microscopy children has also been studied. Although with HAstVs were routinely detected by direct less frequency than rotavirus, , and transmission electron microscopy (EM) in

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negatively stained stool samples (Cubitt et al., radioimmune assay for detection of anti- 1999). This method was the pioneer diagnostic MAstV 1 (serotypes HAstV 1–8) antibodies method but a push for several alternatives was (Wilson and Cubitt, 1988). Several born out of the numerous limitations modifications made possible via the associated with its use. This procedure is development of monoclonal antibodies has laborious, time-consuming, and entails the resulted in the development of Enzyme-linked services of experienced personnel. Secondly, immunosorbent assays and Rapid its sensitivity has been questioned since only immunochromatography tests with good 10% of the viral particle present in stool sensitivity and specificity. These test kits have retains the characteristic star-like shape been commercialized by several companies, necessary for its diagnosis (Madeley, 1979). easy to use, but their usage has been hampered Several techniques have been employed to by the advent of molecular techniques (Pérot increase the sensitivity of electron et al., 2017). microscopy. These methods include Molecular assays concentration of viral particles in stool sample The advent of molecular detection techniques, as well as the use of immune cells based initially on probe hybridization and later (Berthiaume et al., 1981). on genome amplification, opened the Virus isolation possibility to develop assays with exquisite Astroviruses, like other enteric viruses, can be sensitivity and specificity for the diagnosis of difficult to propagate in conventional cell AstVs in stool (Glass et al., 1996). While the cultures. The first propagation of HAstVs was sensitivity of probe hybridization has been made possible by Lee and Kurtz in Human described to be on the same level as that of embryo kidney (HEK) cells through the use of Enzyme ImmunoAssay (EIA), Reverse serum medium supplemented in trypsin (Lee transcriptase PCR (RT-PCR) offers thresholds and Kurtz, 1981). Several cell culture of detection as low as 10 to 100 genome platforms have been studied with a bid to copies per gram of stool (Glass et al.,1996). isolate and gain insight into the pathology of Nevertheless, the sensitivity of these Human Astroviruses, but very few have been molecular assays relies greatly on several able to support the growth of Human variables, such as primer/probe selection, Astroviruses. Presently, adenocarcinoma cell enzymatic amplification reaction conditions, lines, colonic carcinoma cells and human and last but not least, the efficiency of the hepatoma cell line are the commonly used target nucleic acid extraction (Bosch et al., platform used to propagate the growth of 2014). In any case, studies employing EIA and Human Astroviruses (Brinker et al., 2000). RT-PCR in parallel reported a higher number While virus isolation can serve as a useful tool of positive samples scored by the latter to investigate astrovirus biology, it is still not technique as well as a longer period of viral an ideal diagnostic tool for detection of shedding that extended beyond the resolution astrovirus in diagnostic laboratories, due to of symptoms (Mitchell et al., 1995). slow turnaround times and difficulty of Management, prevention and control isolation (Pérot et al., 2017). There is no anti-viral treatment for astrovirus Serology infection, because the rarely The ability to grow astroviruses has simplified required hospitalization. But Bjorkholm et al., the production of antisera in experimental (1995) demonstrated in a study how a 78 years animals, allowing the characterization of old patient diagnosed with Waldenstrom's serotypes and the development of a macroglobulinemia was given 0.4 g/kg of

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astrovirus immunoglobulin for four days, and Potential threat of Zoonotic transmission the symptoms resolved. This led to a full There are several studies that have recovery from the viruses; though, additional documented the existence of interspecies testing is yet to be completed. transmission. Genome similarities have been However, young children who are at risk due reported from several studies that assayed for to preexistent malnutrition or illness are given the relationship between Astroviruses (ORT) which is also recovered from different species (Donato and used for managing Rotavirus infections and Vijaykrishna, 2017). Ecotones (ecological other diarrhoeal diseases like Cholera, to avoid transition areas such as small and medium diarrhoeal dehydration and the serious effects sized farms which rear multiple species) have of gastroenteritis (Bosch et al., 2014). been highlighted as a critical factor The prevention of HAstV infections is responsible for the reported interspecies essentially based on the control of the transmission. The co-rearing of poultry such transmission routes and on the prevention and as domestic ducks, chickens, turkey, and control of disease at the host level. The control guinea fowl can facilitate transmission of the transmission routes includes virus between these species but also transmission to detection and inactivation in water and food, wild birds (Donato and Vijaykrishna, 2017). and disinfection of contaminated fomites Many other species have contact with (Bosch et al., 2014). Individuals infected livestock in a farming environment; in should have their feaces properly disposed far addition to wild species, companion animals away from water bodies. such as cats and dogs and other peri-domestic Prevention of disease development in the host animals have contact with livestock and their includes vaccination and potentiation of the biological waste providing substantial natural defenses such as the gut microbiota. opportunities for cross-species transmission. No vaccines have been developed for HAstVs Farms and abattoirs have also been recognized despite several descriptions of virus-like as environments facilitating transmission particle (VLP) production in different systems between livestock species to farm and abattoir (Mor et al., 2011). This lack of commercial workers. The genome similarity between interest in production may be due to Human Astroviruses and other viruses the low clinical impact of astrovirus infection (members of the corona family) implicated in in healthy patients and to the need for a zoonotic transmission highlights the multivalent vaccine to cover all circulating possibility of Astroviruses zoonotic serotypes and strains or at least the most transmission. prevalent ones, since apparently there is not Conclusion heterologous protection (Bosch et al., 2014). Our understanding of the implication of Some authors have speculated that probiotics, astrovirus infection has greatly benefited from which may interfere with the biological cycle the evolution of technologies, from initial of enteric virus at many different steps, may morphological identification to the most recent be used as a measure to prevent and/or treat advanced high throughput molecular intestinal viral infections (Colbère-Garapin et techniques, regarding especially Human al., 2007) Additionally, the antiviral activity Astroviruses. More attention should be of some synthetic flavonoids on astrovirus channeled into a better understanding of its replication has been described (Bosch et al., virulent factors, disease formation process and 2014). interspecies transmission with a bid to avert the danger of zoonotic transmission.

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Acknowledgement Virol., 91:e01859-16. doi: We sincerely appreciate our amiable 10.1128/JVI.01859-16 Lecturer/Virologist professor Lohya Nimzing Bosch, A., Guix S, Pintó R.M. (2013) and friend Yakubu Ajang all in the University Epidemiology of human astrovirus, p 1– of Jos, Jos Nigeria for their time and 18. In Schultz-Cherry S (ed), Astrovirus contributions. research: essential ideas, everyday impacts, future directions. Springer, References New York, NY. Abad, F.X., Villena C, Guix S, Caballero S, Bosch, A., Pintó R.M, Guix S. (2014) Human Pintó R.M, Bosch A. (2001) "Potential astroviruses. Clin Microbiol role of fomites in the vehicular Review,27(4):1048–74. transmission of human astroviruses". Bosch, A., Guix S., Krishna N.K., Méndez E., Applied and Environmental Monroe S.S., Pantin-Jackwood M., Microbiology, 67 (9): 3904–7. Schultz-Cherry S. (2012) Family— doi:10.1128/AEM.67.9.3904-3907.2001. Astroviridae. In: King A.M.Q., Aminu, M., Ameh E.A., Geyer A, Esona M.D, Lefkowitz E., Adams M.J., Carstens Taylor M.B, Steele A.D. (2009) Role of E.B., editors. Virus Taxonomy: Ninth astrovirus in intussusception in Nigerian Report of the International Committee infants. J. Trop. Pediatr., 55:192–194. on Taxonomy of Viruses. San Diego, doi:10.1093/tropej/fmn101 CA: Elsevier. Appleton, H, Higgins P.G. (1975) Viruses and Brinker, J.P., Blacklow N.R., Herrmann J.E. gastroenteritis in infants. Lancet, i:1297. (2000) Human astrovirus isolation and (Letter) propagation in multiple cell lines. Arch. Berthiaume, L., Alain R., McLaughlin B., Virol., 145:1847–1856. doi: Payment P., Trépanier P. (1981) Rapid 10.1007/s00705007006 detection of human viruses in faeces by Britton, R.A., Versalovic J. (2008) Probiotics a simple and routine immune electron and gastrointestinal infections. microscopy technique. J. Gen. Virol., Interdiscip. Perspect. Infect. Dis., 10. 55:223–227. doi: 10.1099/0022-1317- doi:10.1155/2008/290769. 55-1-223. Colbère-Garapin, F., Martin-Latil S, Blondel Björkholm, M., Celsing F, Runarsson G, B, Mousson L, Pelletier I, Autret A, Waldenström J. (1995) "Successful François A, Niborski V, Grompone G, intravenous immunoglobulin therapy for Catonnet G, van de Moer A. (2007) severe and persistent astrovirus Prevention and treatment of enteric viral gastroenteritis after fludarabine infections: possible benefits of probiotic treatment in a patient with bacteria. Microbes Infect., 9:1623–1631. Waldenström's macroglobulinemia". doi:10.1016/j.micinf.2007.09.016. International Journal of Hematology, 62 Cubitt, W.D., Mitchell D.K, Carter M.J, (2): 117–20. doi:10.1016/0925- Willcocks M.M, Holzel H. (1999) 5710(95)00396-A. PMID 8590772 Application of electronmicroscopy, Bogdanoff, W.A., Campos J., Perez E.I., Yin enzyme immunoassay, and RT-PCR to L., Alexander D.L., DuBois R.M. (2016) monitor an outbreak of astrovirus type 1 Structure of a human astrovirus capsid— in a paediatric bone marrow transplant complex and mechanistic unit. J. Med. Virol., 57:313–321. insights into virus neutralization. J. doi:10.1002/(SICI)1096-

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