Novel human astroviruses in pediatric respiratory samples: A one‐year survey in a Swiss tertiary care hospital

Cordey, Samuel; Zanella, Marie-Céline; Wagner, Noémie; Turin, Lara; Kaiser, Laurent

doi:10.1002/jmv.25246

Cited by 13 publications

(9 citation statements)

References 16 publications

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“…Oral inoculation of mice with 1 ϫ 10 7 infectious particles of HAstV1 or with MLB1 and VA2 fecal filtrates, followed by cohousing with recipient animals, resulted in no virus replication that was detectable by reverse transcription-quantitative PCR (qRT-PCR) in the donor mice or the recipient mice. In view of the recent evidence that the MLB and VA strains are associated with encephalitis and respiratory infections in humans (35,36), we also performed intracisternal magnal and intranasal inoculations; however, inoculation via either of these routes resulted in no productive replication in the 8-to 10-week-old animals. Finally, we administered 1 ϫ 10 6 infectious particles of HAstV1 to 8-week-old mice via intraperitoneal injection.…”

Section: Resultsmentioning

confidence: 99%

“…Attempts to confirm replication by immunofluorescent staining in tissue sections using either a peptide-based rabbit polyclonal serum directed to the virus capsid or a murine antibody that detects double-stranded RNA were unsuccessful. While additional evidence of replication will require further tool development, this finding is notable given the recent evidence that the MLB and VA strains are associated with respiratory symptoms in humans (35,36). These experimental data could indicate that the virus infects a common cell type that is shared between the lung and gut mucosa.…”

Section: Discussionmentioning

confidence: 98%

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Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice

Cortez

Sharp

Yao

et al. 2019

J Virol

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Human astroviruses are single-stranded RNA enteric viruses that cause a spectrum of disease ranging from asymptomatic infection to systemic extragastrointestinal spread; however, they are among the least-characterized enteric viruses, and there is a lack of a well-characterized small animal model. Finding that immunocompromised mice were resistant to human astrovirus infection via multiple routes of inoculation, our studies aimed to determine whether murine astrovirus (MuAstV) could be used to model human astrovirus disease. We experimentally infected wild-type mice with MuAstV isolated from immunocompromised mice and found that the virus was detected throughout the gastrointestinal tract, including the stomach, but was not associated with diarrhea. The virus was also detected in the lung. Although virus levels were higher in recently weaned mice, the levels were similar in male and female adult mice. Using two distinct viruses isolated from different immunocompromised mouse strains, we observed virus strain-specific differences in the duration of infection (3 versus 10 weeks) in wild-type mice, indicating that the within-host immune pressure from donor mice shaped the virus kinetics in immunocompetent recipient hosts. Both virus strains elicited minimal pathology and a lack of sustained immunity. In summary, MuAstV represents a useful model for studying asymptomatic human infection and gaining insight into the astrovirus pathogenesis and immunity. IMPORTANCE Astroviruses are widespread in both birds and mammals; however, little is known about the pathogenesis and the immune response to the virus due to the lack of a well-characterized small-animal model. Here we describe two distinct strains of murine astrovirus that cause infections in immunocompetent mice that mirror aspects of asymptomatic human infections, including minimal pathology and short-lived immunity. However, we noted that the duration of infection differed greatly between the strains, highlighting an important facet of these viruses that was not previously appreciated. The ubiquitous nature and diversity of murine astroviruses coupled with the continuous likelihood of reinfection raise the possibility of viral interference with other mouse models of disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice

Cortez

Sharp

Yao

et al. 2019

J Virol

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“…Novel HAstVs are part of the neurovirulent astroviruses, which also include animal astroviruses (30). Other unexpected clinical manifestations recently associated with human and animal astroviruses include respiratory tract infections (31)(32)(33)(34)(35)(36)(37), fever of unknown etiology (38,39), hepatitis (40,41), and severe gout in geese (42). Altogether, these findings suggest that there are probably other still unrecognized divergent astroviruses with clinical implications beyond gastroenteritis in humans and animals.…”

mentioning

confidence: 94%

Human Astrovirus MLB Replication In Vitro : Persistence in Extraintestinal Cell Lines

Bosch

Pintó

et al. 2019

J Virol

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MLB astroviruses were identified 10 years ago in feces from children with gastroenteritis of unknown etiology and have been unexpectedly detected in severe cases of meningitis/encephalitis, febrile illness of unknown etiology, and respiratory syndromes. The aim of this study was to establish a cell culture system supporting MLB astrovirus replication. We used two clinical strains to infect several cell lines, an MLB1 strain from a gastroenteritis case, and an MLB2 strain associated with a neurologic infection. Efforts to propagate the viruses in the Caco-2 cell line were unsuccessful. In contrast, we identified two human nonintestinal cell lines, Huh-7 and A549, permissive for both genotypes. After serial passages in the Huh-7.5 cell line, the adapted strains were able to establish persistent infections in the Huh-7.5, Huh-7AI, and A549 cell lines, with high viral loads (up to 10 log10 genome copies/ml) detected by quantitative reverse transcription-PCR (RT-qPCR) in the culture supernatant. Immunofluorescence assays demonstrated infection in about 10% of cells in persistently infected cultures. Electron microscopy revealed particles of 32 to 33 nm in diameter after negative staining of cell supernatants and capsid arrays in ultrathin sections with a particularly high production in Huh-7.5 cells. Interferon (IFN) expression by infected cells and effect of exogenous IFN varied depending on the type of infection and the cell line. The availability of a cell culture system to propagate MLB astroviruses represents a key step to better understand their replicative cycle, as well as a source of viruses to conduct a wide variety of basic virologic studies. IMPORTANCE MLB astroviruses are emerging viruses infecting humans. More studies are required to determine their exact epidemiology, but several reports have already identified them as the cause of unexpected clinical diseases, including severe neurologic diseases. Our study provides the first description of a cell culture system for the propagation of MLB astroviruses, enabling the study of their replicative cycle. Moreover, we demonstrated the unknown capacity of MLB astrovirus to establish persistent infections in cell culture. Whether these persistent infections are also established in vivo remains unknown, but the clinical consequences would be of high interest if persistence was confirmed in vivo. Finally, our analysis of IFN expression provides some trails to understand the mechanism by which MLB astroviruses can cause persistent infections in the assayed cultures.

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“…To date, no clear association between astrovirus infection and respiratory diseases has been made, however, several astroviruses have been detected from nasopharyngeal (NP) swabs. All three clades of human astroviruses have been detected from human NP or oral swabs and in some cases were associated with respiratory symptoms [ 19 , 83 , 92 , 126 , 127 , 128 ]. Other mammals have also been positive from NP swabs including camels, pigs, and cattle [ 122 , 129 , 130 , 131 , 132 ].…”

Section: Respiratory Diseasementioning

confidence: 99%

Beyond the Gastrointestinal Tract: The Emerging and Diverse Tissue Tropisms of Astroviruses

Janowski

2021

Viruses

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Astroviruses are single stranded, positive-sense RNA viruses that have been historically associated with diseases of the gastrointestinal tract of vertebrates, including humans. However, there is now a multitude of evidence demonstrating the capacity of these viruses to cause extraintestinal diseases. The most striking causal relationship is neurological diseases in humans, cattle, pigs, and other mammals, caused by astrovirus infection. Astroviruses have also been associated with disseminated infections, localized disease of the liver or kidneys, and there is increasing evidence suggesting a potential tropism to the respiratory tract. This review will discuss the current understanding of the tissue tropisms for astroviruses and their emerging capacity to cause disease in multiple organ systems.

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Novel human astroviruses in pediatric respiratory samples: A one‐year survey in a Swiss tertiary care hospital

Cited by 13 publications

References 16 publications

Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice

Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice

Human Astrovirus MLB Replication In Vitro : Persistence in Extraintestinal Cell Lines

Beyond the Gastrointestinal Tract: The Emerging and Diverse Tissue Tropisms of Astroviruses

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