Acute encephalopathy in an immunocompromised boy with astrovirus-MLB1 infection detected by next generation sequencing

Sato, Masanori; Kuroda, Makoto; Kasai, Masashi; Matsui, Hikoro; Fukuyama, Tetsuhiro; Katano, Harutaka; Tanaka‐Taya, Keiko

doi:10.1016/j.jcv.2016.03.010

Cited by 85 publications

(73 citation statements)

References 26 publications

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“…Although diagnostic PCR assays may exist for some of these viruses, they are unlikely to have been considered in the differential diagnosis and therefore would not be routinely tested. This included two cases of human parvovirus 4 (PARV4), 28 first described in 2005 when it was associated with a viraemic patient in whom an acute viral infection was suspected 49 ; one case of human coronavirus OC-43, 43 typically a human respiratory pathogen never previously described in a human case of encephalitis but known to cause encephalitis in mice 50 ; one case of human astrovirus MLB1, 46 of mumps vaccine virus in a child who was vaccinated prior to a primary immunodeficiency diagnosis. 48 The five cases in which rare causes of encephalitis were identified were Brucella melitensis, Candida tropicalis, Leptospira santarosai and two cases of Balamuthia mandrillaris.…”

Section: Improved Diagnosis With Ngsmentioning

confidence: 99%

Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases

Brown¹,

Bharucha²,

Breuer³

2018

Journal of Infection

206

179

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There is increasing evidence of a role for NGS in the work-up of undiagnosed encephalitis. Lower costs and increasing accessibility of these technologies will facilitate larger studies of these patients. We recommend NGS should be considered as a front-line diagnostic test in chronic and recurring presentations and, given current sample-to-result turn-around times, as second-line in acute cases of encephalitis.

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Section: Improved Diagnosis With Ngsmentioning

confidence: 99%

Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases

Brown¹,

Bharucha²,

Breuer³

2018

Journal of Infection

206

179

View full text Add to dashboard Cite

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“…The case of the immunocompromised patient with the astrovirus encephalitis illustrates the power of HTS in identifying a novel and unexpected virus not previously associated with a CNS infection. Astroviruses are being increasingly recognized as significant neurotropic pathogens in immunocompromised patients [32,33,34,35]. …”

Section: Examples Of Hts In Unexplained Viral Encephalitismentioning

confidence: 99%

Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances

Kennedy

Quan

Lipkin

2017

Viruses

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Viral encephalitis causes acute inflammation of the brain parenchyma and is a significant cause of human morbidity and mortality. Although Herpes Simplex encephalitis is the most frequent known cause of fatal sporadic encephalitis in humans, an increasingly wide range of viruses and other microbial pathogens are implicated. Up to 60% of cases of presumed viral encephalitis remain unexplained due to the failure of conventional laboratory techniques to detect an infectious agent. High-throughput DNA sequencing technologies have the potential to detect any microbial nucleic acid present in a biological specimen without any prior knowledge of the target sequence. While there remain challenges intrinsic to these technologies, they have great promise in virus discovery in unexplained encephalitis.

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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).…”

mentioning

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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Acute encephalopathy in an immunocompromised boy with astrovirus-MLB1 infection detected by next generation sequencing

Cited by 85 publications

References 26 publications

Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases

Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases

Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances

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

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