Astroviruses
Authors: Dorsey M. Bass, M.D. , Harry B. Greenberg, M.D.
Virology
Astroviruses has been assigned to their own family, the Astroviridae, despite a physical similarity to caliciviruses, because of their unique genomic organization and antigenic structure. Like Norwalk virus, astroviruses form 28-30-nm particles that contain a single positive-stranded, polyadenylated, genomic RNA. During cellular infection, a large number of copies of subgenomic RNA are made which encode the structural capsid proteins of the virus. Approximately 10% of particles in stool display a characteristic solid five- or six-pointed star by electron microscopy (EM), which contrasts with the hollow-centered stars often seen on caliciviruses. Astroviruses contain three major structural proteins and can be grown in tissue culture with added trypsin under conditions similar to those used for propagating rotaviruses. Immunologic studies have identified eight distinct serotypes of human astrovirus, all of which appear to cause diarrheal illness. Recently two new distinct groups of human astroviruses have been described –MLB and -VA/HMO (2, 5, 6). Although both groups were originally associated with pediatric gastroenteritis, their full role in human disease requires further study.
Epidemiology
Astroviruses have been found to be a significant pathogen in young children with diarrhea and predominantly infects children less than 2 years of age (4, 9, 14, 15). Several studies have suggested that very young infants are particularly susceptible (15). Astroviruses have also been associated with foodborne outbreaks of gastroenteritis in Japanese adults and school children (13). Astroviruses appear to account for 4 to 8.6% of all young children with diarrhea, depending on geographic location. Infections occur primarily in winter time in temperate climates, as has been reported for rotavirus. Studies have shown that astroviruses can cause sporadic outbreaks of diarrhea in elderly patients and that it is significantly associated with diarrheal illness in immunocompromised AIDS patients (7), solid organ transplant recipients , and bone marrow transplant recipients (3).
Clinical Manifestations
The clinical illness caused by astrovirus in children is similar to that caused by rotavirus, with a high incidence of fever and diarrhea. The illness is, in general, considerably milder, however; and causes less dehydration than rotavirus infection. The range of symptoms also seems to vary from location to location; an outbreak in Guatemala was characterized by a lower frequency of vomiting and fever than an outbreak in Thailand (7, 9). Astrovirus illness is considerably less pathogenic in young adult volunteers, with only 5% of infected individuals developing clinical symptoms, presumably due to pre existing immunity. The increased incidence of astrovirus illness in elderly patients suggests that immunity is acquired in childhood and wanes later in life. In premature infants, infection has been associated with necrotizing enterocolitis but whether this association is causal remains unknown.
Laboratory Diagnosis
Both EM and immunoelectron microscopy (IEM) have been used to diagnose astrovirus infection, because of the high levels of viral shedding feces (1010 particles/mL). Misclassification of astrovirus as calicivirus is common using these methods because typical astrovirus morphology is present in only 10% of particles, and microscopists may not be experienced enough to detect it. Commercial enzyme-linked immunosorbent assays (ELISAs) have been developed that are highly specific for astrovirus and have been used in diagnosis of children with diarrheal illness (10). RNA probes and polymerase chain reaction (PCR) methods have also been developed for both detection and serotyping of astroviruses and have proven useful for confirmation of ELISA results (10, 12).
Pathogenesis
Astrovirus pathogenesis has not been well studied in humans. Viral particles have been visualized by EM in intestinal epithelial cells and in epithelial cells located in the lower part of the villi, suggesting that the intestine is the site of replication. Astrovirus pathogenesis has been studied in lambs and calves, using ovine and bovine astrovirus isolates, respectively. Infection of lambs induces a mild transient diarrhea that occurs 2 days after infection and lasts approximately 2 days. Infection of calves with at least one strain of bovine astrovirus did not induce diarrheal illness, although the infection was associated with sloughing of infected villus cells.
SUSCEPTIBILITY IN VITRO AND IN VIVO
No model has been established for susceptibility testing for astrovirus. Several attempts to infect small laboratory animals with human astrovirus isolates have been unsuccessful. Murine astroviruses are common in laboratory mice but have not been associated with diarrheal illness.
ANTIMICROBIAL THERAPY
At this time, no effective antiviral therapy exists for astrovirus.
ADJUNCTIVE THERAPY
Very few published reports exist on the use of directed therapeutic efforts for the treatment of astrovirus-associated gastroenteritis. Many of the same strategies that have been attempted for treating rotavirus gastroenteritis are also being examined for treating astrovirus gastroenteritis, though with limited success. In one case, a patient with Waldenstrom's macroglobulinemia who developed astrovirus diarrhea during a course of cytoreductive therapy responded to treatment with intravenous immunoglobulin (1). Although treatment eliminated diarrheal symptoms, viral shedding continued for more than 2 weeks after therapy was initiated. Possibly, as the study of these viruses continues, we will improve our ability to make specific antibodies and be able to conduct further tests on their therapeutic efficacy.
VACCINES
There are no vaccines available.
REFERENCES
1. Bjorkholm M, Celsing F, Runarsson G, Waldenstrom J. Successful intravenous immunoglobulin therapy for severe and persistent astrovirus gastroenteritis after fludarabine treatment in a patient with Waldenstrom's macroglobulinemia. Int J Hematol 1995; 62:117-120. [PubMed]
2. Bosch A, Pintó RA, Guix S. Human Astroviruses. Clin. Microbiol. Rev.2014;27:1048. [PubMed]
3. Cox GJ, Matsui SM, Lo RS, Hinds M, Bowden RA, Hackman RC, Meyer WG, Mori M, Tarr PI, Oshiro LS: Etiology and outcome of diarrhea after marrow transplantation: a prospective study. Gastroenterology 1994;107:1398-1407. [PubMed]
4. Cruz JR, Bartlett AV, Herrmann JE, Caceres P, Blacklow NR, Cano F. Astrovirus-associated diarrhea among Guatemalan ambulatory rural children. J Clin Microbiol 1992;30:1140-1144. [PubMed]
5. Finkbeiner SR, Kirkwood CD, Wang D. Complete genome sequence of a highly divergent astrovirus isolated from a child with acute diarrhea. Virol J, 2008;5:117. [PubMed]
6. Finkbeiner SR, Li Y, Ruone S, Conrardy C, Gregoricus N, Toney D, Tong S. Identification of a novel astrovirus (astrovirus VA1) associated with an outbreak of acute gastroenteritis. Journal of Virology, 2009;83:10836-10839. [PubMed]
7. Gonzalez GG, Pujol FH, Liprandi F, Deibis L, Ludert JE. Prevalence of enteric viruses in human immunodeficiency virus seropositive patients in Venezuela. Journal of Medical Virology 1998; 55:288-292. [PubMed]
8. Herrmann JE, Nowak NA, Perron-Henry DM, Hudson RW, Cubitt WD, Blacklow NR. Diagnosis of astrovirus gastroenteritis by antigen detection with monoclonal antibodies. J Infect Dis 1990;161:226-229. [PubMed]
9. Herrmann JE, Taylor DN, Echeverria P, Blacklow NR: Astroviruses as a cause of gastroenteritis in children. [PubMed]
10. Jonassen TO, Monceyron C, Lee TW, Kurtz JB, Grinde B: Detection of all serotypes of human astrovirus by the polymerase chain reaction. J Virol Methods 1995;52:327-334. [PubMed]
11. Kapoor A, Li L, Victoria J, Oderinde B, Mason C, Pandey P, Zaidi SZ, Delwart E. Multiple novel astrovirus species in human stool. J Gen Virol 2009;90:2965–2972. [PubMed]
12. Noel JS, Lee TW, Kurtz JB, Glass RI, Monroe SS: Typing of human astroviruses from clinical isolates by enzyme immunoassay and nucleotide sequencing. J Clin Microbiol 1995;33:797-801. [PubMed]
13. Oishi I, Yamazaki K, Kimoto T, Minekawa Y, Utagawa E, Yamazaki S, Inouye S, Grohmann GS, Monroe SS, Stine SE A large outbreak of acute gastroenteritis associated with astrovirus among students and teachers in Osaka, Japan. J Infect Dis 1994;170:439-443. [PubMed]
14. Palombo EA Bishop RF: Annual incidence, serotype distribution, and genetic diversity of human astrovirus isolates from hospitalized children in Melbourne, Australia. J Clin Microbiol 1996; 34:1750-1753. [PubMed]
15. Shastri S, Doane AM, Gonzales J, Upadhyayula U, Bass DM. Prevalence of astroviruses in a children's hospital. J Clin Microbiol 1998;36:2571-2574. [PubMed]
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