Distribution and clinical associations of ljungan virus (Parechovirus B)

Cristina Fevola

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Among rodent-borne viruses, those belonging to the genera Mammarenavirus, Orthohantavirus and Orthopoxvirus are a particular focus of study both in humans and animals, since they represent some of the most widespread rodent-borne disease-causing pathogens. More recently, the interest in parechoviruses has been increasing because some are known to cause diseases in humans, while others are carried by rodents, although the zoonotic potential of rodent-borne parechoviruses has not been established. Ljungan virus (LV), which belongs to the species Parechovirus B, was first isolated from bank voles in Sweden in 1998. It belongs to the Picornaviridae family. Currently, there is little information about LV host range and epidemiology, but a few reports suggest an association between LV and human disease. The main aims of this doctoral thesis were to establish the symptoms associated with LV in humans, to investigate the association of LV with human central nervous system (CNS) disease, and to determine the prevalence and distribution of LV in human and other animal populations in Europe. LV-associated symptoms were investigated in two human cohorts. Serum samples from Finnish patients hospitalized for suspected nephropathia epidemica (NE) caused by the Orthohantavirus Puumala virus (PUUV) were screened for the presence of lymphocytic choriomeningitis virus (LCMV, Arenavirus), cowpox virus (CPXV, Orthopoxvirus) and LV, in order to compare the disease outcomes in these patients and to establish if the co-existence of viruses could lead to an increase in the severity of symptoms. However, no unusual or additional manifestations between PUUV cases and PUUV-LV/LCMV/CPXV cases were detected. To determine if LV (together with the rodent-borne virus LCMV) could be one of the causes of neurological symptoms in Finnish patients with suspected CNS disease, anti-LV and LCMV antibodies were analyzed from serum and cerebrospinal fluid samples. LV- and LCMV-specific nucleic acids were also analyzed from the patient samples. However, no association between LV or LCMV antibodies or nucleic acids and the neurological manifestations in the patient cohort was detected. In order to improve the knowledge of the host and geographical distribution of LV, tissues from multiple rodent and insectivore species from ten European countries were screened for LV nucleic acids. We confirmed that LV is widespread geographically, having been detected in at least one host species in nine out of ten countries involved in the study. Seventeen out of 21 species screened were LV PCR-positive. Results indicated that bank voles are the main rodent host for LV. Male and subadult bank voles are significantly more likely to be LV-positive, and the prevalence has a temporal pattern (higher in autumn compared to spring and summer), possibly due to adult bank voles clearing the infection.
Original languageEnglish
Supervisors/Advisors
  • Jääskeläinen, Anne J, Supervisor
  • Vaheri, Antti, Supervisor
  • Hauffe, Heidi C., Supervisor, External person
Award date11 Jan 2019
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-4748-6
Electronic ISBNs978-951-51-4749-3
Publication statusPublished - 2019
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • Parechovirus
  • Picornaviridae Infections
  • Hantavirus Infections
  • Rodentia
  • Arenaviridae Infections
  • Orthopoxvirus
  • Poxviridae Infections
  • Central Nervous System Diseases
  • +virology
  • Hemorrhagic Fever with Renal Syndrome
  • Puumala virus
  • Lymphocytic choriomeningitis virus
  • Cowpox virus
  • Arvicolinae
  • Host-Pathogen Interactions
  • Sweden
  • Europe
  • Genome, Viral
  • Disease Transmission, Infectious
  • Virulence
  • 3111 Biomedicine
  • 3121 Internal medicine

Cite this

Fevola, C. (2019). Distribution and clinical associations of ljungan virus (Parechovirus B). Helsinki : Helsingin yliopisto.
Fevola, Cristina. / Distribution and clinical associations of ljungan virus (Parechovirus B). Helsinki : Helsingin yliopisto, 2019. 82 p.
@phdthesis{3904821fffd84facba9f3d9dad523477,
title = "Distribution and clinical associations of ljungan virus (Parechovirus B)",
abstract = "Among rodent-borne viruses, those belonging to the genera Mammarenavirus, Orthohantavirus and Orthopoxvirus are a particular focus of study both in humans and animals, since they represent some of the most widespread rodent-borne disease-causing pathogens. More recently, the interest in parechoviruses has been increasing because some are known to cause diseases in humans, while others are carried by rodents, although the zoonotic potential of rodent-borne parechoviruses has not been established. Ljungan virus (LV), which belongs to the species Parechovirus B, was first isolated from bank voles in Sweden in 1998. It belongs to the Picornaviridae family. Currently, there is little information about LV host range and epidemiology, but a few reports suggest an association between LV and human disease. The main aims of this doctoral thesis were to establish the symptoms associated with LV in humans, to investigate the association of LV with human central nervous system (CNS) disease, and to determine the prevalence and distribution of LV in human and other animal populations in Europe. LV-associated symptoms were investigated in two human cohorts. Serum samples from Finnish patients hospitalized for suspected nephropathia epidemica (NE) caused by the Orthohantavirus Puumala virus (PUUV) were screened for the presence of lymphocytic choriomeningitis virus (LCMV, Arenavirus), cowpox virus (CPXV, Orthopoxvirus) and LV, in order to compare the disease outcomes in these patients and to establish if the co-existence of viruses could lead to an increase in the severity of symptoms. However, no unusual or additional manifestations between PUUV cases and PUUV-LV/LCMV/CPXV cases were detected. To determine if LV (together with the rodent-borne virus LCMV) could be one of the causes of neurological symptoms in Finnish patients with suspected CNS disease, anti-LV and LCMV antibodies were analyzed from serum and cerebrospinal fluid samples. LV- and LCMV-specific nucleic acids were also analyzed from the patient samples. However, no association between LV or LCMV antibodies or nucleic acids and the neurological manifestations in the patient cohort was detected. In order to improve the knowledge of the host and geographical distribution of LV, tissues from multiple rodent and insectivore species from ten European countries were screened for LV nucleic acids. We confirmed that LV is widespread geographically, having been detected in at least one host species in nine out of ten countries involved in the study. Seventeen out of 21 species screened were LV PCR-positive. Results indicated that bank voles are the main rodent host for LV. Male and subadult bank voles are significantly more likely to be LV-positive, and the prevalence has a temporal pattern (higher in autumn compared to spring and summer), possibly due to adult bank voles clearing the infection.",
keywords = "Parechovirus, Picornaviridae Infections, Hantavirus Infections, Rodentia, Arenaviridae Infections, Orthopoxvirus, Poxviridae Infections, Central Nervous System Diseases, +virology, Hemorrhagic Fever with Renal Syndrome, Puumala virus, Lymphocytic choriomeningitis virus, Cowpox virus, Arvicolinae, Host-Pathogen Interactions, Sweden, Europe, Genome, Viral, Disease Transmission, Infectious, Virulence, 3111 Biomedicine, 3121 Internal medicine",
author = "Cristina Fevola",
note = "M1 - 82 s. + liitteet",
year = "2019",
language = "English",
isbn = "978-951-51-4748-6",
series = "Dissertationes scholae doctoralis ad sanitatem investigandam Universitatis Helsinkiensis",
publisher = "Helsingin yliopisto",
number = "1/2019",
address = "Finland",

}

Distribution and clinical associations of ljungan virus (Parechovirus B). / Fevola, Cristina.

Helsinki : Helsingin yliopisto, 2019. 82 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Distribution and clinical associations of ljungan virus (Parechovirus B)

AU - Fevola, Cristina

N1 - M1 - 82 s. + liitteet

PY - 2019

Y1 - 2019

N2 - Among rodent-borne viruses, those belonging to the genera Mammarenavirus, Orthohantavirus and Orthopoxvirus are a particular focus of study both in humans and animals, since they represent some of the most widespread rodent-borne disease-causing pathogens. More recently, the interest in parechoviruses has been increasing because some are known to cause diseases in humans, while others are carried by rodents, although the zoonotic potential of rodent-borne parechoviruses has not been established. Ljungan virus (LV), which belongs to the species Parechovirus B, was first isolated from bank voles in Sweden in 1998. It belongs to the Picornaviridae family. Currently, there is little information about LV host range and epidemiology, but a few reports suggest an association between LV and human disease. The main aims of this doctoral thesis were to establish the symptoms associated with LV in humans, to investigate the association of LV with human central nervous system (CNS) disease, and to determine the prevalence and distribution of LV in human and other animal populations in Europe. LV-associated symptoms were investigated in two human cohorts. Serum samples from Finnish patients hospitalized for suspected nephropathia epidemica (NE) caused by the Orthohantavirus Puumala virus (PUUV) were screened for the presence of lymphocytic choriomeningitis virus (LCMV, Arenavirus), cowpox virus (CPXV, Orthopoxvirus) and LV, in order to compare the disease outcomes in these patients and to establish if the co-existence of viruses could lead to an increase in the severity of symptoms. However, no unusual or additional manifestations between PUUV cases and PUUV-LV/LCMV/CPXV cases were detected. To determine if LV (together with the rodent-borne virus LCMV) could be one of the causes of neurological symptoms in Finnish patients with suspected CNS disease, anti-LV and LCMV antibodies were analyzed from serum and cerebrospinal fluid samples. LV- and LCMV-specific nucleic acids were also analyzed from the patient samples. However, no association between LV or LCMV antibodies or nucleic acids and the neurological manifestations in the patient cohort was detected. In order to improve the knowledge of the host and geographical distribution of LV, tissues from multiple rodent and insectivore species from ten European countries were screened for LV nucleic acids. We confirmed that LV is widespread geographically, having been detected in at least one host species in nine out of ten countries involved in the study. Seventeen out of 21 species screened were LV PCR-positive. Results indicated that bank voles are the main rodent host for LV. Male and subadult bank voles are significantly more likely to be LV-positive, and the prevalence has a temporal pattern (higher in autumn compared to spring and summer), possibly due to adult bank voles clearing the infection.

AB - Among rodent-borne viruses, those belonging to the genera Mammarenavirus, Orthohantavirus and Orthopoxvirus are a particular focus of study both in humans and animals, since they represent some of the most widespread rodent-borne disease-causing pathogens. More recently, the interest in parechoviruses has been increasing because some are known to cause diseases in humans, while others are carried by rodents, although the zoonotic potential of rodent-borne parechoviruses has not been established. Ljungan virus (LV), which belongs to the species Parechovirus B, was first isolated from bank voles in Sweden in 1998. It belongs to the Picornaviridae family. Currently, there is little information about LV host range and epidemiology, but a few reports suggest an association between LV and human disease. The main aims of this doctoral thesis were to establish the symptoms associated with LV in humans, to investigate the association of LV with human central nervous system (CNS) disease, and to determine the prevalence and distribution of LV in human and other animal populations in Europe. LV-associated symptoms were investigated in two human cohorts. Serum samples from Finnish patients hospitalized for suspected nephropathia epidemica (NE) caused by the Orthohantavirus Puumala virus (PUUV) were screened for the presence of lymphocytic choriomeningitis virus (LCMV, Arenavirus), cowpox virus (CPXV, Orthopoxvirus) and LV, in order to compare the disease outcomes in these patients and to establish if the co-existence of viruses could lead to an increase in the severity of symptoms. However, no unusual or additional manifestations between PUUV cases and PUUV-LV/LCMV/CPXV cases were detected. To determine if LV (together with the rodent-borne virus LCMV) could be one of the causes of neurological symptoms in Finnish patients with suspected CNS disease, anti-LV and LCMV antibodies were analyzed from serum and cerebrospinal fluid samples. LV- and LCMV-specific nucleic acids were also analyzed from the patient samples. However, no association between LV or LCMV antibodies or nucleic acids and the neurological manifestations in the patient cohort was detected. In order to improve the knowledge of the host and geographical distribution of LV, tissues from multiple rodent and insectivore species from ten European countries were screened for LV nucleic acids. We confirmed that LV is widespread geographically, having been detected in at least one host species in nine out of ten countries involved in the study. Seventeen out of 21 species screened were LV PCR-positive. Results indicated that bank voles are the main rodent host for LV. Male and subadult bank voles are significantly more likely to be LV-positive, and the prevalence has a temporal pattern (higher in autumn compared to spring and summer), possibly due to adult bank voles clearing the infection.

KW - Parechovirus

KW - Picornaviridae Infections

KW - Hantavirus Infections

KW - Rodentia

KW - Arenaviridae Infections

KW - Orthopoxvirus

KW - Poxviridae Infections

KW - Central Nervous System Diseases

KW - +virology

KW - Hemorrhagic Fever with Renal Syndrome

KW - Puumala virus

KW - Lymphocytic choriomeningitis virus

KW - Cowpox virus

KW - Arvicolinae

KW - Host-Pathogen Interactions

KW - Sweden

KW - Europe

KW - Genome, Viral

KW - Disease Transmission, Infectious

KW - Virulence

KW - 3111 Biomedicine

KW - 3121 Internal medicine

M3 - Doctoral Thesis

SN - 978-951-51-4748-6

T3 - Dissertationes scholae doctoralis ad sanitatem investigandam Universitatis Helsinkiensis

PB - Helsingin yliopisto

CY - Helsinki

ER -

Fevola C. Distribution and clinical associations of ljungan virus (Parechovirus B). Helsinki : Helsingin yliopisto, 2019. 82 p. (Dissertationes scholae doctoralis ad sanitatem investigandam Universitatis Helsinkiensis; 1/2019 ).