Human Astrovirus Infection in a Patient with New-Onset Celiac Disease

Abstract

Many diseases with unknown etiology may be caused by unidentified viruses. Sequence-independent amplification revealed a new astrovirus, similar to VA1, in a 4-year-old male diagnosed with celiac disease. This expands the geographic range of this virus to include Europe and may associate astrovirus infection with the onset of celiac disease.Infectious diseases pose a continuous disease burden on humans, and many diseases with unknown etiology may be caused by unidentified viruses. Key to effectively counter the potential public health threat caused by emerging infectious diseases requires a systematic exploration of infectious viruses. Diarrhea is a common cause of morbidity and mortality. In developing countries, the mortality associated with gastroenteritis has been estimated at 3 to 5 million cases per year (24). In industrialized countries, although typically self-limited, diarrheal diseases are a significant cause of morbidity among all age groups. Most gastroenteritis cases in industrialized countries are caused by viruses (24). However, the etiological cause of a large proportion of diarrhea cases (up to ϳ40%) remains unresolved. The implementation of new technologies for virus discovery, based on microarrays or sequence-independent amplification of nucleic acids, already resulted in identification of many previously unknown viruses, among which are several new human astroviruses in human stool samples (1, 2, 5-9, 11, 14-16, 19-21, 23).From the Diagnostic Unit, Department of Virology, Erasmus Medical Center, Rotterdam, Netherlands, we received 84 diarrhea samples of unknown etiology for further analysis on the potential presence of viral pathogens. Random sequence-independent amplification of RNA on an initial subset of these samples revealed the presence of new picobirnaviruses and a rhinovirus (22) and was now also performed on diarrhea from patient VS34. A total of 138 clones were sequenced, and most of the sequences were unclassified or of bacterial origin. Three out of 138 clones contained sequences most closely related to mink and ovine astroviruses by BLASTn similarity searches (3).To acquire the 3Ј ϳ4,400 bp of the astrovirus genome, the astrovirus sequence reads from a stool sample from patient VS34 were assembled in different contigs and the nucleic acid between the contigs was obtained by reverse transcriptase-PCR (RT-PCR) with 400 nM primers VS474 and VS475 ( Fig. 1; Table 1), 1ϫ AmpliTaq Gold reaction buffer, 2.5 mM MgCl 2 , 200 M each deoxynucleoside triphosphates (dNTPs), and 2.5 U AmpliTaq Gold with Geneamp (Roche). The conditions for amplification were 95°C for 5 min, followed by 40 cycles of 95°C for 30 s, 50°C for 1 min, and 72°C for 1 min, followed by a single incubation at 72°C for 10 min. In addition, 3Ј rapid amplification of cDNA ends (RACE) PCR was employed, using primers VS430, VS431, VS457, VS432, and VS458 ( Fig. 1; Table 1), as described previously (22). Amino acid sequences from open reading frame 1b (ORF1b) and ORF2 of the astrovirus from sample VS34 were aligned to the re...

Wastewater Analysis Indicates that Genetically Diverse Astroviruses, Including Strains Belonging to Novel Clades MLB and VA, Are Circulating within Japanese Populations

“…The presence of these novel AstVs has been documented in several countries, including Australia, China, India, Nepal, the Netherlands, Nigeria, Pakistan, and the United States, but not in Japan (19,20,22,23,47,48). We identified MLB-AstVs in all influent samples collected between November 2007 and March 2008.…”

Human Astroviruses

“…Serological studies in the United States have confirmed that HAstV-HMO-C (VA1) is a highly prevalent human-infectious agent (115). In a recent study, a strain closely related to HAstV-VA1 was isolated in a patient with new-onset celiac disease (114). Finally, similarly to what has been observed for classic HAstVs, extraintestinal dissemination in immunodeficient individuals has also been observed in HAstV-HMO-C (VA1) virus infections, when the agent was detected in neural tissue from an immunocompromised child with encephalitis (116).…”

“…HAstV-VA/HMO (VA1, VA2, and VA3 [also known as HMO-C, HMO-A, and HMO-B, respectively] and VA4) have been detected in pediatric gastroenteritis samples in Nigeria, Nepal, and Pakistan (29), the United States (27), Egypt (107), and China (109), but so far they have never been reported in Europe (114). Serological studies in the United States have confirmed that HAstV-HMO-C (VA1) is a highly prevalent human-infectious agent (115).…”

“…Although these primers should be able to detect all known human and animal AstVs, so far they have allowed the detection of both classic and novel human AstVs (107,110). Primers designed to specifically detect HAstV-MLB and HAstV-VA/HMO have also been described (27,30,114).…”

Impact of the birth’s season on the development of celiac disease in Italy

“…However, as reported in other autoimmune diseases [2,7,9,29,31], there is emerging evidence in favor of the importance of nondietary environmental factors in the later CD and especially the role of environmental factors related to the season of birth. In particular, the infectious diseases caused by rotavirus and astrovirus [30,32,37] as well as the fluctuating vitamin D level might be reflected in a seasonal variation in CD risk related to month of birth [19,28,34].…”