Astrovirus

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Astrovirus
Astrovirus 4.jpg
Electron micrograph of Astroviruses
Virus classification
Group: Group IV ((+)ssRNA)
Family: Astroviridae
Genus & Species

Genus: Avastrovirus

Avian nephritis virus
Chicken astrovirus
Duck astrovirus
Turkey astrovirus

Genus: Mamastrovirus

Bovine astrovirus
Capreolus capreolus astrovirus
Feline astrovirus
Human astrovirus
Ovine astrovirus
Mink astrovirus
Porcine astrovirus

Astrovirus is a type of virus that was first discovered in 1975 using electron microscopes following an outbreak of diarrhea in humans.[1] In addition to humans, astroviruses have now been isolated from numerous mammalian animal species (and are classified as genus Mammoastrovirus) and from avian species such as ducks, chickens, and turkey poults (classified as genus Aviastrovirus). Astroviruses are 28–35 nm diameter, icosahedral viruses that have a characteristic five- or sixpointed 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.[2] Astrovirus has a non-segmented, single stranded, positive sense RNA genome within a non-enveloped icosahedral capsid.[3] Human astroviruses have been shown in numerous studies to be an important cause of gastroenteritis in young children worldwide.[2]

Signs and symptoms in humans[edit]

Members of a relatively new virus family, the astroviridae, astroviruses are now recognised as a cause of gastroenteritis in children, whose immune systems are underdeveloped, and elderly adults, whose immune systems are generally somewhat comprised. Presence of viral particles in fecal matter and in epithelial intestinal cells indicate that the virus replicates in the gastrointestinal tract of humans.[4] The main symptoms are diarrhoea, followed by nausea, vomiting, fever, malaise and abdominal pain. Some research studies have shown that the incubation period of the disease is approximately three to four days. Astrovirus infection is not usually a severe situation and only in some rare cases leads to dehydration. The severity and variation in symptoms correlates with the region the case develops in. This could be due to climatic factors influencing the life cycle or transmission method for that particular strain of Astrovirus. Malnutrition and immunodeficiency tend to exasperate the condition, leading to more severe cases or secondary conditions that could require hospital care.[5] Otherwise, infected people do not need hospitalization because symptoms will reduce by themselves, after 2 to 4 days.[6]

Diagnosis[edit]

Electron microscopy, enzyme-immunoassay (ELISA), immunofluorescence, and polymerase chain reaction have all been used for detecting virus particle, antigens or viral nucleic acid in the stools of infected people.[7] A method using real-time RT-PCR, which can detect all human astrovirus genotypes, has been reported.[8]

Pathogenesis[edit]

Astroviruses cause gastroenteritis by causing destruction of the intestinal epithelium, leading to the inhibition of usual absorption mechanism, loss of secretory functions, and decrease in epithelial permeability in the intestines. Inflammatory responses were seen to not have an impact on astrovirus pathogenesis. [9]

Epidemiology[edit]

A study of intestinal disease in the UK, published in 1999, determined incidence as 3.8/1000 patient years in the community (95% CI, range 2.3–6.4), the fourth most common known cause of viral gastroenteritis.[10] Studies in the USA have detected astroviruses in the stools of 2–9% of children presenting symptoms; illness is most frequent in children younger than two years, although outbreaks among adults and the elderly have been reported. Early studies carried out in Glasgow demonstrated that a significant proportion of babies excreting virus particles, 12%, did not exhibit gastrointestinal symptoms; seroprevalence studies carried out in the US have shown that 90% of children have antibody to HastV-1 by age 9, suggesting that (largely asymptomatic) infection is common. There is, as with most viral causes of gastroenteritis, a peak of incidence in the winter.[11]

Humans of all ages are susceptible to astrovirus infection, but children, the elderly, and those that are immunocompromised are most prone. The majority of children have acquired astrovirus antibodies by the age of 5 and, looking at the pattern of disease, it suggests that antibodies provide protection through adult life, until the antibody titre begins to decline later in life.[12][13]

Astroviruses are associated with 5–9% of cases of gastroenteritis in young children.[14] The occurrence of astrovirus infection varies depending on the season. In temperate climates infection is highest during winter months. This is in contrast to tropical regions where prevalence is highest during the rainy season. This seasonal distribution of infection in temperate climates is rather puzzling. But the seasonal distribution in tropical climates can be explained by the impact of the rain particularly on breakdown of sanitation in developing countries.[11]

The main mode of astrovirus transmission is by contaminated food and water. Young children in childcare backgrounds or adults in military barracks are most likely to develop the disease.

Timeline[edit]

1975: Appleton and Higgins first discovered astrovirus in stool samples of children suffering from gastroenteritis by using electron microscopy (EM)

1975: Madeley and Cosgrove named the 20-30 nm viral particle Astrovirus based on the star-like EM (electron microscopy) appearance

1976-1992: Lee and Kurtz serotyped 291 astrovirus stool samples in Oxford; discovered serotypes 6 and 7

1981: Lee and Kurtz were able to grow astrovirus in tripsin-dependent tissue culture by using human embryo kidney cells (HEK)

1985: Lee and Kurtz discover two serotypes of astrovirus that are used to type 13 strains of community-aquired astrovirus

1987: Gray et al. discovered that a 22 day long gastroenteritis outbreak in an elderly home was caused by astrovirus type 1 and calicivirus

1988: Hermann and Hudson use antigen characterization of HEK grown astroviruses to develop monoclonal antibodies

1992: Cruz et al. analyzed 5,000 stool samples 7.5% of the diarrheal diseases found in Guatemalan ambulatory rural children were caused by astroviruses

1993: Jiang et al. sequence astrovirus RNA and determine the presence of three ORFs and ribosomal frameshifting

1993: Monroe et al. classify subgenomic data for astrovirus, providing support for astrovirus to be classified as a viral family

1994: Oishi et al. determine astrovirus as the main cause of gastroenteritis in schools in Katano City, Osaka, Japan

1995: Bjorkholm elt al. conducted a clinical study, and 78-year-old male Waldenström's macroglobulinemia patient with astrovirus-associated gastroenteritis was successfully treated with intravenous immunoglobulin

1995: Jonassen et al. uses PCR to detect all known serotypes (7) of astrovirus

1995: In their sixth report, ICTV establishes Astroviridae as a viral family

1996: Glass et al. states an epidemiological shift regarding astrovirus due to improvements in RT-PCT (reverse transcription PCR), monoclonal antibodies, and enzyme immunoassays (EIA); astroviruses are now considered one of the main causes of diarrheal disease worldwide

1996: Palombo and Bishop the epidemiology of astrovirus infections in children suffering from gastroenteritis in Melbourne, Australia (data collected include total incidence, genetic diversity, serotype characterization)

1998: Unicomb et al. conduct a clinical study in Bangladesh and conclude astrovirus infections involving nosocomial, acute, and persistent diarrheal diseases

1998: Gaggero et al. identify human astrovirus type 1 to be the main cause of acute gastroenteritis in Chilean children

1999: Bon et al. discover astrovirus in a gastroenteritis outbreak in Dijon, France

2001: Dennehy et al. collected stool samples from hospitalized children suffereing from acute gastroenteritis; astrovirus was determined the second leading cause of gastroenteritis after rotavirus

2002: Guix et al. completes an epidemiological study on the presence of astrovirus in Barcelona, Spain; the total incidence of astrovirus in 2,347 samples was 4.95 with a peak in the number of cases in the winter

2003: Basu et al. discovered astrovirus in 2.7% of stool samples collected from 346 children suffering from gastroenteritis in Gaborone, Botswana

2009: Finkbeiner et al. used Sanger sequencing to discover a novel astrovirus in stool samples from children suffering from an acute gastroenteritis outbreak at a childcare center

2009: Using RT-PCR, Kapoor et al. discover novel astrovirus strains HMOAstV species A, B, C which are very similar to astroviruses found in mink and ovine species; this showed that the virus may have the ability to jump species

Prevention[edit]

Inactivated vaccines are in use for certain strains of Chicken Astrovirus (CastV).

Treatment[edit]

First Drug Profile: Astrovirus Immunoglobulin In a study by Bjorkholm et al., a 78 year old patient diagnosed with Waldenstrom's macroglobulinemia was given 0.4 g/kg of astrovirus immunoglobulin for four days, and the symptoms dissolved leading to a full recovery from astrovirus; however, further testing has yet to be completed. [15]

Second Drug Profile: Achyrocline Bogotensis Antiviral Therapy In a study by Tellez et al, extracts from a plant Achyrocline Bogotensis was used to develop an antiviral therapy for both rotavirus and astrovirus. Achyrocline Bogotensis was commonly used for skin and urinary infections. Drug testing methodology involved application of the extract to cell for pre-treatment (blocking), direct viral activity (evidence of killing the virus), and treatment (a decrease in the viral load after an infection is established). The extract demonstrated direct viral activity by killing astroviruses directly and treatment by leading to a decrease in the viral load after an established infection. A pre-treatment effect was not evidence during the experiment. [16]

Microbiology[edit]

Taxonomic structure[edit]

-Group: ssRNA(+)

[17] The family Astroviridae contains two genera: Mamastroviruses which infect mammals and Avastroviruses which infect birds. In each genus, there are species of astroviruses, each named after the host in which they replicate. The astroviruses are further subclassified within each species into serotypes.[18]

There are at least three genotypes of bovine astroviruses.[19] These appear to be related to the Capreolus capreolus astrovirus.

Virus structure[edit]

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.[20]

Genus Structure Symmetry Capsid Genomic Arrangement Genomic Segmentation
Avastrovirus Icosahedral T=3 Non-Enveloped Linear Monopartite
Mamastrovirus Icosahedral T=3 Non-Enveloped Linear Monopartite

[21]

Human astrovirus structure: 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.[22]

Life Cycle[edit]

Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription, using an unknown model of subgenomic RNA transcription is the method of transcription. Translation takes place by -1 ribosomal frameshifting. Vertebrates serve as the natural host. Transmission routes are fecal-oral.[21]

Genus Host Details Tissue Tropism Entry Details Release Details Replication Site Assembly Site Transmission
Avastrovirus Birds Enterocytes Cell receptor endocytosis Budding Cytoplasm Cytoplasm Oral-fecal
Mamastrovirus Humans; mammals Enterocytes Cell receptor endocytosis Budding Cytoplasm Cytoplasm Oral-fecal

Genome[edit]

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. With the exclusion of polyadenylation at the 3' end, the genome is between 6.8–7.9 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.[23] 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.[24]

The 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.[25]

Evolution[edit]

The Astroviridae capsid is related to those of the Tymoviridae.[26] The non-structural region is related to the Potyviridae. It appears that this group of viruses may have arise at some point in the past as a result of recombination event between two distinct viruses and that this even occurred at the junction of the structural and non structural coding regions.

Species infected[edit]

In addition to humans, goats, cattle, pigs, wild boar, sheep, roe deer, bats, sea lions, rats, and mice are known to be infected with these viruses.[27][28][29]

Recent Findings[edit]

January 24th, 2017: Human astrovirus (particularly serotypes 1, 4, 6, and 8) were found in 4.2% of the of samples collected from children suffering from acute gastroenteritis in Nara Prefecture, Japan [30]

February 2017: Cortez et al. conducted a retrospective study on persistent infections in pediatric oncology patients and determined human astrovirus to be the main cause of gastroenteritis in immunocompromised patients[31]

April 2017 (electronically published December 28th, 2016): Bennett and Gunson developed a novel multiplex RT-PCR diagnostic technique to detect the presence of a variety of inflectional intestinal diseases (IID) including astrovirus, adenovirus, rotavirus, and sapovirus from stool samples [32]

December 2016: Yuan et al. discovered that the recovery rate for astroviruses was 8.24% for a novel centrifugal method developed to concentrate human enterviruses from water samples [33]

December 18th, 2016: Lum et al. demonstrated the capacity of human astrovirus (particularly Neuroinvasive astrovirus (VA1-HMO-C)) to become an emerging opportunistic infection. An 8-month-old bone marrow transplant patient died of VA1/HMO-C encephalitis following the transplant. The presence of VA1/HMO-C was confirmed after positive PCR test results. [34]

References[edit]

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