Astrovirus MLB2, a New Gastroenteric Virus Associated with Meningitis and Disseminated Infection

Cordey, Samuel; Vu, Diem‐Lan; Schibler, Manuel; L’Huillier, Arnaud G.; Brito, Francisco; Docquier, Mylène; Posfay‐Barbe, Klara M.; Petty, Tom J.; Turin, Lara; Zdobnov, Evgeny M.; Kaiser, Laurent

doi:10.3201/eid2205.151807

Cited by 112 publications

(98 citation statements)

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“…In humans, cases of meningoencephalitis associated with human astrovirus 4, astrovirus MLB1, and MLB2 have been described (37)(38)(39). In minks, an astrovirus genotype is the causative agent of shaking mink syndrome, a neurological disorder of minks characterized by tremors and seizures (40,41).…”

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confidence: 99%

Propagation of Astrovirus VA1, a Neurotropic Human Astrovirus, in Cell Culture

Janowski

Bauer

Holtz

et al. 2017

J Virol

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Astrovirus VA1/HMO-C (VA1; mamastrovirus 9) is a recently discovered astrovirus genotype that is divergent from the classic human astroviruses (mamastrovirus 1). The gastrointestinal tract is presumed to be the primary site of infection and pathogenicity for astroviruses. However, VA1 has been independently detected in brain tissue of five cases of human encephalitis. Studies of the pathogenicity of VA1 are currently impossible because there are no reported cell culture systems or in vivo models that support VA1 infection. Here, we describe successful propagation of VA1 in multiple human cell lines. The initial inoculum, a filtered clinical stool sample from the index gastroenteritis case cluster that led to the discovery of VA1, was first passaged in Vero cells. Serial blind passage in Caco-2 cells yielded increasing copies of VA1 RNA, and multistep growth curves demonstrated a Ͼ100-fold increase in VA1 RNA 72 h after inoculation. The full-length genomic and subgenomic RNA strands were detected by Northern blotting, and crystalline lattices of viral particles of ϳ26-nm diameter were observed by electron microscopy in infected Caco-2 cells. Unlike other human astrovirus cell culture systems, which require addition of exogenous trypsin for continued propagation, VA1 could be propagated equally well with or without the addition of trypsin. Furthermore, VA1 was sensitive to the type I interferon (IFN-I) response, as VA1 RNA levels were reduced by pretreatment of Caco-2 cells with IFN-␤1a. The ability to propagate VA1 in cell culture will facilitate studies of the neurotropism and neuropathogenesis of VA1.IMPORTANCE Astroviruses are an emerging cause of central nervous system infections in mammals, and astrovirus VA1/HMO-C is the most prevalent astrovirus in cases of human encephalitis. This virus has not been previously propagated, preventing elucidation of the biology of this virus. We describe the first cell culture system for VA1, a key step necessary for the study of its ability to cause disease.KEYWORDS astrovirus, astrovirus VA1, cell culture, electron microscopy, encephalitis, pathogenesis, subgenomic RNA, viral propagation I nitially identified in 1975, members of the single-stranded, positive-sense RNA viral family Astroviridae have been frequently detected in vertebrate stool samples (1, 2). In humans, the first identified astrovirus species was mamastrovirus 1 (classic human astrovirus), and eight serotypes of this virus have been described (2-4). Most humans are exposed to the classic human astroviruses with seroprevalence as high as 94% to specific serotypes (5-9). The classic human astroviruses predominantly cause a selflimited gastrointestinal illness and have been characterized as the third-to fifth-mostcommon viral etiology of diarrhea and gastroenteritis in humans (10)(11)(12)(13)(14).Astroviruses contain three open reading frames (ORFs) and based on conserved genomic elements are hypothesized to share common mechanisms of replication (2). Astroviruses encode a slippery sequence and stem-...

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confidence: 99%

Propagation of Astrovirus VA1, a Neurotropic Human Astrovirus, in Cell Culture

Janowski

Bauer

Holtz

et al. 2017

J Virol

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“…AstV MLB2 was first detected in human stool samples from India and the United States in 2009 [11]. This virus was subsequently found in febrile children from USA [12], children with diarrhea from Japan and Turkey [13, 14], and patients with meningitis [11].…”

Section: Resultsmentioning

confidence: 99%

“…This virus was subsequently found in febrile children from USA [12], children with diarrhea from Japan and Turkey [13, 14], and patients with meningitis [11]. However, no previous studies mentioned discovering AstV MLB2 from animals.…”

Section: Resultsmentioning

confidence: 99%

Viral metagenomics of fecal samples from non-human primates revealed human astrovirus in a chimpanzee, China

et al. 2016

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BackgroundHuman astroviruses (HAstVs) are commonly identified worldwide as important aetiological agents of acute gastroenteritis in all age groups. More and more evidences challenged the paradigm that AstV infections are species-specific. Yet to date, AstVs associated with human infections have not been detected in any animal hosts.ResultsViral metagenomics methods were used to detect viral nucleic acids in fecal samples from 69 captive non-human primates (NHPs) from three zoos in China. Sequence reads showing high similarity to astrovirus MLB2 were found in feces from a chimpanzee with diarrhea. The complete genome of this astrovirus was determined and deposited in the GenBank under accession number KX273058 (named SAstV-nj). Phylogenetic analysis based on complete genomes revealed that SAstV-nj was closely related to and shared >98% nucleotide sequence identity with the previous human astrovirus MLB2 strains.ConclusionsThis study suggested that MLB2-related astroviruses might have the potential of cross-species transmission between human and NHP.

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“…When brain specimens were available, pathological examination provided proof of diagnosis of encephalitis. CSF analysis results were reported in 25 patients of 20 studies, with the white blood cell count ranging from 1 to 494 cell/mm 3 in encephalitis and meningoencephalitis cases and 915 cell/mm 3 in the only meningitis case [22]; three publications reported normal CSF analysis without any description [23e25]. HTS was performed on individual CSF and brain specimens in 129 and 21 patients, respectively.…”

Section: Clinical Samples Analysed With Htsmentioning

confidence: 99%

“…HTS allowed the identification of viruses previously unknown or unexpected as a cause of CNS infection (n ¼ 10) and thus not screened during diagnostic investigations (Table 1). These included parvovirus 4 (two) [46], human coronavirus OC43 (one) [25], and novel HAstV-MLB2 (one) [22] identified in immunocompetent patients. A mumps virus vaccine strain (one) [41], HAstV (undetermined specie; one) [47], HAstV-VA1 (four) [23,31,33,43], and HAstV-MLB1 (one) [24] were identified in immunocompromised patients.…”

Section: Virus Identification With Htsmentioning

confidence: 99%

High-throughput sequencing for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis. A narrative review and clinical appraisal

Zanella

Lenggenhager

Schrenzel

et al. 2019

Clinical Microbiology and Infection

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a b s t r a c tBackground: Viral aetiologies are the most common cause of central nervous system (CNS) infections. Approximately one-half of CNS infections remain of undetermined origin. High-throughput sequencing (HTS) brought new perspectives to CNS infection investigations, allowing investigation of viral aetiologies with an unbiased approach. HTS use is still limited to specific clinical situations. Objectives: The aim of this review was to evaluate the contribution and pitfalls of HTS for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis in CNS patient samples. Sources: PubMed was searched from 1 January 2008 to 2 August 2018 to retrieve available studies on the topic. Additional publications were included from a review of full-text sources. Content: Among 366 studies retrieved, 29 used HTS as a diagnostic technique. HTS was performed in cerebrospinal fluid and brain biopsy samples of 307 patients, including immunocompromised, immunocompetent paediatric, and adult cases. HTS was performed retrospectively in 18 studies and prospectively in 11. HTS led to the identification of a potential causal virus in 41 patients, with 11 viruses known and ten not expected to cause CNS infections. Various HTS protocols were used. Implications: The additional value of HTS is difficult to quantify because of various biases. Nevertheless, HTS led to the identification of a viral cause in 13% of encephalitis, meningoencephalitis, and meningitis cases in which various assays failed to identify the cause. HTS should be considered early in clinical management as a complement to routine assays. Standardized strategies and systematic studies are needed for the integration of HTS in clinical management. M.-C. Zanella, Clin Microbiol Infect 2019;25:422

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Astrovirus MLB2, a New Gastroenteric Virus Associated with Meningitis and Disseminated Infection

Abstract: This virus is an unrecognized cause of central nervous system infection, particularly among immunocompromised patients.

Cited by 112 publications

References 35 publications

Propagation of Astrovirus VA1, a Neurotropic Human Astrovirus, in Cell Culture

Propagation of Astrovirus VA1, a Neurotropic Human Astrovirus, in Cell Culture

Viral metagenomics of fecal samples from non-human primates revealed human astrovirus in a chimpanzee, China

High-throughput sequencing for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis. A narrative review and clinical appraisal

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