Astroviridae

Classification & Taxonomy:

screen-shot-2015-03-19-at-2-35-53-amClassification used to be based only on the host of origin; a new classification scheme has been proposed based on the amino acid sequence of Open Reading Frame 2 (this encodes for the capsid polyprotein & has the most variance in the genome).

Family: Astroviridae, Genera: Avastrovirus, MamastrovirusThey are single stranded, positive sense RNA viruses and are monopartiteThey are nonenvelopedThe capsid morphology is icosahedralThey are the second or third most common cause of viral diarrhea in young children.Have been isolated from humans, pigs, cats, minks, sheep, calfs, dogs, bats, rats, deer, and marine mammals such as dolphins and sea lions (these of the Mamastrovirus). Of the Avastrovirus, the virus has been isolated from ducks, chickens, turkeys, and guinea fowl.

It has T=3 icosahedral symmetry. The capsid is about 35 nm, spikes protrude from 30 vertices. The cellular tropism: enterocytes / epithelial cells of the intestinal tract.


Molecular Biology

Virus.Replication occurs in the cytoplasm

  1. There is attachment to host receptors, which mediates the endocytosis of the virus into host cell.
  2. There is uncoating and subsequent release of the viral genomic RNA into the cytoplasm
  3. The RNA is translated into two polyproteins to create replication proteins, which happens in the Endoplasmic Reticulum (double stranded RNA genome is created from the positive single stranded RNA).
  4. Subgenomic RNA translation creates the capsid precursor
  5. Assembly of the new virions
  6. Maturation of the capsid and non-lytic virus release

The organization of the astrovirus genome places the Open Reading Frames encoding the structural proteins at the 3’ end and the nonstructural proteins at the 5’ end. Other distinctive features of the family include the lack of a DNA-helicase, and the usage of ribosomal frameshifting as a mechanism to translate the RNA –dependent RNA polymerase.


Transmission and Pathogenesis

v54The transmission is fecal-oral. This means it is transmitted via contaminated water and food, as well as through person to person contact (seen in an outbreak of gastroenteritis in California). Illnesses in adults can also happen as a result of a large exposure to astrovirus or through fomites.It is partially resistant to chlorination, which is widely used for wastewater treatment in many countries.

Most astrovirus infections in humans are detected in the winter months (in temperate regions) and in the rainy season (in tropical climates).Incubation period: 3-4 daysAssociated diseases: gastroenteritis, celiac disease, intussusception (Fields 622).Symptoms: diarrhea in 72% – 100% in all cases, duration from 2-3 daysAbdominal pain: 50%Vomiting: 20% – 70%Fever : 20% -25%Maximum fever: 37.9 ºC Hospitalization: 6%, duration of 6 days on average.


Treatment & Diagnostic Tools

Treatment: astrovirus usually results in a self-limiting illness that does not require hospitalization. Oral (or intravenous) Rehydration Therapy may be necessary. IVIV may also help in those with immunocompromisation.Diagnostic tools: Enzyme Immuno-Assay (EIA), electron microscopy, and reverse transcription-polymerase chain reaction (RT-PCR).


Prevention & Management

There is no vaccine for any of the serotypes. However, inoculation of the recombinant, baculovirus-expressed capsid protein to hens partially protected the offspring for the presence of gut lesions à potential for vaccine candidates for humans.Interruption of transmission is the key factor in preventing astrovirus infection (especially in hospitals and other institutions, day care centers and families).It is resistant in part to chlorination and to normal disinfectants, therefore universal hygienic procedures must be enforced in these settings.


Updates on Astroviruses 2014 – 2015

AstrovirusNovel human astroviruses: challenges for developing countries:

Astroviruses have been gaining widespread importance over the past few decades owing to their detection through advanced molecular techniques. The association of astrovirus-associated enteric infections have been reported from various settings among different age groups. The tremendous efforts of scientists from different countries to detect and characterize these star-like viruses in the course of surveillance has shown the emergence of novel astroviruses from varied host species, necessitating changes in the classification to update their taxonomy. The public health importance of these viruses implies new control measures are essential to reduce disease burden in developing countries.Astrovirus VA1/HMO-C: An Increasingly Recognized Neurotropic Pathogen in Immunocompromised Patients:

An 18-month-old boy developed encephalopathy, for which extensive investigation failed to identify an etiology, 6 weeks after stem cell transplant. To exclude a potential infectious cause, we performed high-throughput RNA sequencing on brain biopsy.

RNA-Seq was performed on an Illumina Miseq, generating 20 million paired-end reads. Nonhost data were checked for similarity to known organisms using BLASTx. The full viral genome was sequenced by primer walking.

We identified an astrovirus, HAstV-VA1/HMO-C-UK1(a), which was highly divergent from human astrovirus (HAstV 1-8) genotypes, but closely related to VA1/HMO-C astroviruses, including one recovered from a case of fatal encephalitis in an immunosuppressed child. The virus was detected in stool and serum, with highest levels in brain and cerebrospinal fluid (CSF). Immunohistochemistry of the brain biopsy showed positive neuronal staining. A survey of 680 stool and 349 CSF samples identified a related virus in the stool of another immunosuppressed child.

The discovery of HAstV-VA1/HMO-C-UK1(a) as the cause of encephalitis in this case provides further evidence that VA1/HMO-C viruses, unlike HAstV 1-8, are neuropathic, particularly in immunocompromised patients, and should be considered in the differential diagnosis of encephalopathy. With a turnaround from sample receipt to result of

images-1Rapid and simultaneous detection of three major diarrhea-causing viruses by multiplex real-time nucleic acid sequence-based amplification:

Rotaviruses, noroviruses and astroviruses are the major viral pathogens leading to diarrhea worldwide. Epidemiological investigations of outbreaks associated with these viruses have been impeded by the lack of methods for quick diagnosis and detection. In the current study, a multiplex real-time nucleic acid sequence-based amplification (RT-NASBA) system was developed for the simultaneous detection of rotavirus A/norovirus genogroup II/astrovirus. The specificity and sensitivity of the assay were compared with multiplex RT-PCR. The results showed that the multiplex RT-NASBA assay was established successfully, and robust signals could be observed in 10 minutes with high specificity. The limit of detection of the multiplex RT-NASBA assay was 7, 100, and 200 copies per reaction for rotavirus A, norovirus genogroup II, and astrovirus, respectively. The assay was thus 10 to 100 times more sensitive than multiplex RT-PCR. Clinical evaluation indicated that the assay was 100% concordant with multiplex RT-PCR and was reliable for the detection of both single infections and multiple infections in stool samples. To the best of our knowledge, this is the first multiplex RT-NASBA assay established for the detection of three major diarrhea-causing viruses. This assay provides a valuable platform for the rapid, specific, sensitive and simultaneous diagnosis of these pathogens, especially in resource-limited countries where expensive thermocycling equipment is not available.Genetic heterogeneity and recombination in type-3 human astroviruses:

Human astroviruses (HAstV) are important enteric pathogens and can be classified genetically and antigenically into eight types. During molecular surveillance for human astroviruses in Italy, sequence analysis of the diagnostic region C (about 400 nucleotide in length), located on the capsid (ORF2) gene, identified a novel type-3 strain. Upon sequencing of the full-length ORF2, the type-3 HAstV strain was characterized as a novel ORF2 genetic lineage, designated as 3c. By converse, in the ORF1b the virus was more similar to type-1 HAstVs, rather than to type-3 strains, suggesting a recombination nature, with the crossover site being mapped to the ORF1b/ORF2 junction region. Region C sequences of similar type-3 HAstV identified from European and extra-European countries were retrieved in the databases, suggesting the global distribution of this novel type-3 lineage


Sources:

“Human Astroviruses.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 19 Mar. 2015.

Knipe, David M., and Bernard N. Fields. “Chapter 21: Astroviridae.” Fields’ Virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2013. 609-28. Print.

“ViralZone: Astroviridae.” ViralZone: Astroviridae. ExPASy, n.d. Web. 19 Mar. 2015.

http://www.ncbi.nlm.nih.gov/pubmed/25784567

“Human Astroviruses.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 19 Mar. 2015.Knipe, David M., and Bernard N. Fields. “Chapter 21: Astroviridae.” Fields’ Virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2013. 609-28. Print.“ViralZone: Astroviridae.” ViralZone: Astroviridae. ExPASy, n.d. Web. 19 Mar. 2015.

Works Cited“Human Astroviruses.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 19 Mar. 2015.Knipe, David M., and Bernard N. Fields. “Chapter 21: Astroviridae.” Fields’ Virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2013. 609-28. Print.“ViralZone: Astroviridae.” ViralZone: Astroviridae. ExPASy, n.d. Web. 19 Mar. 2015.

Works Cited“Human Astroviruses.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 19 Mar. 2015.Knipe, David M., and Bernard N. Fields. “Chapter 21: Astroviridae.” Fields’ Virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2013. 609-28. Print.“ViralZone: Astroviridae.” ViralZone: Astroviridae. ExPASy, n.d. Web. 19 Mar. 2015.

Works Cited“Human Astroviruses.” National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 19 Mar. 2015.Knipe, David M., and Bernard N. Fields. “Chapter 21: Astroviridae.” Fields’ Virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2013. 609-28. Print.“ViralZone: Astroviridae.” ViralZone: Astroviridae. ExPASy, n.d. Web. 19 Mar. 2015

http://www.ncbi.nlm.nih.gov/pubmed/25674587

http://www.ncbi.nlm.nih.gov/pubmed/25559674

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