Evolution of echovirus 11 in a chronically infected immunodeficient patient

Laassri, Majid; Zagorodnyaya, Tatiana; Hassin‐Baer, Sharon; Handsher, Rachel; Sofer, Danit; Weil, Merav; Karagiannis, Konstantinos; Simonyan, Vahan; Chumakov, Konstantin; Shulman, Lester M.

doi:10.1371/journal.ppat.1006943

Cited by 8 publications

(10 citation statements)

References 40 publications

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“…The role of cytokines in echovirus pathogenesis in humans is not known. However, immunodeficient individuals, including adults, are more susceptible to echovirus infections, which often induces hepatitis [33][34][35][36]. In addition, analysis of mutations in the E11 genome induced by selective pressure in an immunodeficient individual who developed chronic infection revealed strikingly high sequence conservation in the 3C virally-encoded protease which often attenuates host cell innate immune signaling [36].…”

Section: Plos Pathogensmentioning

confidence: 99%

“…However, immunodeficient individuals, including adults, are more susceptible to echovirus infections, which often induces hepatitis [33][34][35][36]. In addition, analysis of mutations in the E11 genome induced by selective pressure in an immunodeficient individual who developed chronic infection revealed strikingly high sequence conservation in the 3C virally-encoded protease which often attenuates host cell innate immune signaling [36]. Our studies suggest that type I IFNs are the primary drivers of resistance to echovirus infections in the liver, which is supported by our RNASeq studies, in which low levels of the transcripts for type III IFNs were upregulated by infection.…”

Section: Plos Pathogensmentioning

confidence: 99%

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Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice

et al. 2021

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Neonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. However, expression of hFcRn in mice deficient in type I interferon (IFN) signaling, hFcRn-IFNAR-/-, recapitulate the echovirus pathogenesis observed in humans. Luminex-based multianalyte profiling from E11 infected hFcRn-IFNAR-/- mice revealed a robust systemic immune response to infection, including the induction of type I IFNs. Furthermore, similar to the severe hepatitis observed in humans, E11 infection in hFcRn-IFNAR-/- mice caused profound liver damage. Our findings define the host factors involved in echovirus pathogenesis and establish in vivo models that recapitulate echovirus disease in humans.

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Section: Plos Pathogensmentioning

confidence: 99%

Section: Plos Pathogensmentioning

confidence: 99%

Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice

et al. 2021

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“…We next examined children with multiple EV-B infections (i.e., >1 positive sample) and asked if these are multiple positive stools for the same strain of one serotype, which would indicate a prolonged shedding period lasting more than 30 days. The definition of "same virus strain" within a serotype was set as a RNA sequence homology >98% (i.e., evolution rate of acquired mutations during chronic EV-B infection 12 ). The same EV-B serotype strain in more than one positive sample was observed in 11.8% (45/383) of cases and 6.5% (25/383) of controls.…”

mentioning

confidence: 99%

Prospective virome analyses in young children at increased genetic risk for type 1 diabetes

Vehik

Lynch

Wong

et al. 2019

Nat Med

184

220

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“…However, enterovirus infections can be particularly problematic in patients with a weakened immune system. Indeed, studies have shown that some enteroviruses can persist for years in the body and can be continually shed in faeces ( Laassri et al. 2018 ).…”

Section: Introductionmentioning

confidence: 99%

“…Little is known about the persistence of EV-C104 in patients. However, poliovirus, one of the most well-studied group C enteroviruses, has been known to persist in the body for over 30 years ( Laassri et al. 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

Cassidy¹,

Schuele

Lizarazo-Forero

et al. 2022

Virus Evolution

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Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10−3 substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient.

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Evolution of echovirus 11 in a chronically infected immunodeficient patient

Cited by 8 publications

References 40 publications

Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice

Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice

Prospective virome analyses in young children at increased genetic risk for type 1 diabetes

Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

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