Tad Henry 

Humans and Viruses II 155V

Stanford University

Professor Robert Siegel

Winter 2008

Astroviridae: The Facts 



Electron micrograph of astrovirus with

 characteristic starlike appearance

     Classification:

            Family: Astroviridae

            Genera: Mamastrovirus – infects mammals, including humans

                        Avastrovirus – infects avian species

            Viruses: 8 human serotypes: HAstV-1 to HAstV-8

 

Astroviridae Family Basics: 

-Virions have a characteristic starlike surface structure (5 or 6 points) when viewed in an electron           microscope (hence the name; the Greek word “astron” means star)

-The genome is non-segmented positive-sense single stranded RNA

-Icosahedral morphology of the capsid

-Nonenveloped virions

-Virions are 28 to 30 nm in diameter

-Astroviruses have been isolated from numerous species: birds, cats, dogs, pigs, sheep, cows, and                 humans.

-In most mammals, astrovirus infection leads to gastroenteritis

*Human astrovirus is the second leading cause of viral diarrhea in children (after rotavirus of the             family reoviridae)

 


A colorized electron micrograph


Molecular Biology:

The astrovirus genome is approximately 6800 nucleotides of positive single stranded RNA.  The RNA has a polyA tail at the 3’ end but no 5’ end cap. The two open reading frames encoding the nonstructural proteins (ORF1a and ORF1b) are at the 5’ end of the genome, and the open reading frame encoding the structural proteins (ORF2) is at the 3’ end.  ORF2 encodes for 3 proteins that compose the capsid of astrovirus.  ORF1a is believed to encode for the viral protease and ORF1b encodes for RNA-dependent RNA polymerase.   

 

Transmission: Fecal-oral (i.e., virus is passed via contaminated food and water)

Astroviruses are resistant to dessication and can survive for extended periods of time on inert surfaces. Human astroviruses have been detected in multiple types of water sources, including drinking water, rivers, dams, wastewater and effluents from water treatment plants.  Multiple serotypes can be found in a single water sample.  Human astrovirus can survive in water after chlorination.

 

 

 

Diagnosis:

-Electron microscopy, immunofluorescence, enzyme-immunoassay (ELISA), and PCR

 

Clinical Picture:

-Incubation Period: 3 to 4 days

-Human astroviruses are prominent culprits of gastroenteritis cases worldwide

*Symptoms: diarrhea (72-100%), abdominal pain (50%), vomiting (20-70%), fever (20-25%),                  dehydration (24-30%)

-Duration of diarrhea is 2-3 days on average; diarrhea is never bloody

-Hospitalization rates are about 6%

-In general, astrovirus diarrhea is less severe than rotavirus diarrhea and results in fewer                            hospitalizations.

-Death is very rare but cases have been reported.

 

Treatment:  

 Disease caused by human astrovirus is usually not serious enough to require any specific therapy.  However, if diarrhea is particularly acute, oral or intravenous rehydration therapy may be necessary.  Intravenous immunoglobulin may help in severely immunocompromised patients.

 

Prevention and Control:

- There is currently no vaccine for human astrovirus (for any of the serotypes).

- Interruption of transmission is crucial in limiting the spread of human astrovirus.  This is especially        important in hospitals, daycare centers, and in family settings.

-Outbreaks have often been associated with shellfish contamination.

-Universal hygienic procedures must be enforced in all settings--that is, thorough hand washing after       using the bathroom or changing a diaper and before preparing or consuming food.

 

Epidemiology:

Astrovirus predominantly besets young children around the world.  In general, serotype 1 (HAstV-1) is the most common virus found in children.  The majority of children by the age of 5 have acquired astrovirus antibodies, providing protection throughout adult life. Also commonly afflicted are the elderly, military personnel, institutionalized patients, and immunocompromised individuals.  Individuals with HIV, congenital T-cell immunodeficiency, chronic lymphocytic leukemia, and Waldenstrom’s macroglobulinemia are particularly vulnerable to human astroviruses.  Bone marrow transplant recipients and patients treated with fludarabine, know to deplete CD4+ T cells, are also very susceptible.  

Human astrovirus incidence is highest during the winter months in temperate climates and during the rainy season in more tropical climates.

 

New Findings in 2007/8:

 

1) Moser et al. examined the effect of human astrovirus infection on intestinal barrier permeability, an in vitro predictor of diarrhea.  The findings illustrated that astrovirus increased permeability in polarized cells and decreased barrier function. UV-inactivated virus and recombinant virus-like particles also increased barrier permeability.

http://jvi.asm.org/cgi/content/full/81/21/11937


 2) A study by Gabbay et al. describes the first cases of human astrovirus type 8 (HAstV-8) detected in Belem-Brazil.  The strain was compared with other HAstV-8 strains elsewhere in the world and slight differences in the nucleotide sequences were found: In ORF1a, homology values of 93-100 percent were detected and in ORF2 homology values were 96-99 percent.  Considering the sequence variation in ORF2 (7%), it has been suggested that HAstV-8 strains could be divided into three lineages. 

http://www.scielo.br/scielo.php?pid=S0074-02762007000400016&script=sci_arttext&tlng=en

 

3) A study by Liu et al. sheds light on an astrovirus outbreak in Wuhan, China.  Stool specimens from 335 children with diarrhea were taken; 33 of the children (9.87%) were positive for astrovirus RNA. Analysis demonstrated that 23 out of 24 astroviruses identified were genotype 1 (HAstV-1), with highest identity (>98%) to a Mongolian strain.  A vaccine for HAstV-1 would thus be very effective in the Wuhan, China area.

http://jcm.asm.org/cgi/content/full/45/4/1308

 

4) A study by Marshall et al. indicates that HAstV-1 is the most common human astrovirus strain in outbreaks among the elderly.  The outbreak under investigation was in Victoria, Australia in October, 2005.  12 individuals of 86 susceptible residents at the aged-care center became ill during the outbreak.  The mean duration of illness was 2.3 +/- 1.6 days, and symptoms included diarrhea, abdominal pain, nausea and headache. HAstV-1 was the only gastroenteritis virus detected in fecal specimens. 

http://www.springerlink.com/content/x3232168g7213724/fulltext.pdf

 

5) A Kiula et al. study looked at incidence of human astrovirus in children under the age of 10 in Kenya from February 1999 to September 2005. Stool samples were collected from 476 children from clinics in Nairobi and the Maua Methodist Hospital in Meru North, Kenya.  HAstV rates were found to be 6.3%.  There was a higher prevalence in children less than the age of 5 (5.3%) in comparison to those over the age of 5 (0.2%). Also, a higher prevalence of HAstV infections were found in Nairobi (an urban setting) compared to Maua (a rural setting)—5.8 versus 3.7 %.

http://tropej.oxfordjournals.org/cgi/content/abstract/53/3/206 

  

Timeline of Astroviridae in History:

https://www.stanford.edu/dept/humbio/cgi-bin/webauth/wa_login.php?destination=node/1197?sentTid=101


 Links to more astrovirus basic facts:

http://www.nlv.ch/Astrovirus/Astrofactsheet.htm 

http://virology-online.com/viruses/Diarrhoea4.htm 

http://www.microbiologybytes.com/virology/Astroviruses.html 

http://aapredbook.aappublications.org/cgi/content/full/2003/1/3.10 

http://www.virology.net/Big_Virology/BVRNAastro.html 

 

Link to other student astrovirus webpages (and other viral families):

http://www.stanford.edu/group/virus/viruslist.html 

 

A selection of scholarly articles:

 

Abad, F., R. Pinto, C. Villena, R. Gajardo, and A. Bosch. 1997. Astrovirus survival in drinking water. Applied and Environmental Microbiology 63: 3119-3122. 

http://aem.asm.org/cgi/content/abstract/63/8/3119 

   

Koci, M., L. Kelley, D. Larsen, and S. Schultz-Cherry. 2004. Astrovirus-induced synthesis of nitric oxide contributes to virus control during infection. Journal of Virology78: 1564-1574. 

http://jvi.asm.org/cgi/content/full/78/3/1564 

 

Koci, M., L. Moser, L. Kelley, D. Larsen, C. Brown, and S. Schultz-Cherry. 2003. Astrovirus induces diarrhea in the absence of inflammation and cell death. Journal of Virology 77: 11798-11808. 

http://jvi.asm.org/cgi/content/full/77/21/11798 

 

Utagawa, E., S. Nishizawa, S. Sekine, Y. Hayashi, Y. Ishihara, I. Oishi, A. Awasaki, I. Yamashita, K. Miyamura, and S. Yamakazi. 1994. Astrovirus as a cause of gastroenteritis in Japan. Journal of Clinical Microbiology 32 (8): 1841-5. 

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=263888  

 

 Link to several pathogen cards: Central European Encephalitis Virus (CEEV); Murray Valley                     Encephalitis Virus (MVEV);  TT Virus; Sabia Virus (Brazilian Hemorrhagic Fever)

http://tadthenry.googlepages.com/pathogencards 

 


The family dog Astro from The Jetsons


 Bibliography:   

 

Coller, Leslie and John Oxford. Human Virology 2nd Edition. Oxford University Press, 2000: pp. 95-6.

 

Knipe, D., P. Howley, D. Griffin, R. Lamb, and M. Martin.  Fields Virology 5th Edition. Lipincott                         Williams and Wilkins, 2006: pp. 981-998.

 

Narayan, N. Microbiology and Immunology On-line: University of South Carolina School of Medicine.                 2004. Ch. 17: Rotaviruses and other viral agents of gastroenteritis.

    <http://pathmicro.med.sc.edu/virol/rotaviruses.htm>