Parainfluenza Virus Infection

Infectious Disease MONDO:0100197 Pathograph 3 Show in embeddings browser Viral Respiratory Infection

Parainfluenza virus infection is an acute respiratory infection caused by the human parainfluenza viruses (HPIV; enveloped, negative-sense single-stranded RNA viruses of the family Paramyxoviridae), divided antigenically and genetically into types 1 to 4. HPIV-1 to HPIV-3 are major causes of upper and lower respiratory tract infection in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each type tends to cause somewhat distinct illness: HPIV-1 (and HPIV-2) are the leading viral causes of croup (laryngotracheobronchitis), while HPIV-3 is an important cause of bronchiolitis and pneumonia in infancy, second only to respiratory syncytial virus. The virus infects the ciliated respiratory epithelium and elicits an innate antiviral/interferon and inflammatory response that drives much of the symptomatic illness.

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2
Pathophys.
6
Phenotypes
3
Pathograph
2
Medical Actions
1
Datasets
⚙

Pathophysiology

2
Respiratory Epithelial Infection and Innate Immune Response
HPIV infects the ciliated epithelium of the upper and lower respiratory tract, where viral replication is sensed by the host innate immune system and triggers a type I/III interferon and inflammatory cytokine response. Much of the symptomatic illness reflects this host antiviral and inflammatory response together with epithelial injury. HPIV-1 to HPIV-3 are leading causes of lower respiratory tract infection in young children and other vulnerable hosts.
respiratory epithelial cell CL:0002632 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves respiratory epithelial cell, annotated with epithelial cell of lower respiratory tract (CL:0002632). CL:0002632 is a cell type from the Cell Ontology. ciliated airway epithelial cell CL:0000064 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves ciliated airway epithelial cell, annotated with ciliated cell (CL:0000064). CL:0000064 is a cell type from the Cell Ontology.
viral genome replication GO:0019079 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves viral genome replication (GO:0019079). GO:0019079 is a biological process from the Gene Ontology. defense response to virus GO:0051607 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves defense response to virus (GO:0051607). GO:0051607 is a biological process from the Gene Ontology. inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
respiratory system UBERON:0001004 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in respiratory system (UBERON:0001004). UBERON:0001004 is an anatomical location from the Uberon multi-species anatomy ontology. lung UBERON:0002048 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lung (UBERON:0002048). UBERON:0002048 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Laryngotracheal Inflammation and Subglottic Narrowing In the larynx and subglottic airway, HPIV (especially type 1) infection and inflammation narrow the airway, producing croup.
Show evidence (2 references)
PMID:12692097 SUPPORT Other
"HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly."
Establishes HPIV-1 to HPIV-3 as major causes of lower respiratory tract infection in vulnerable hosts. Evidence source is OTHER as this is a review article.
PMID:12692097 SUPPORT Other
"These viruses belong to the Paramyxoviridae family"
Identifies HPIV as members of the Paramyxoviridae family. Evidence source is OTHER as this is a review article.
Laryngotracheal Inflammation and Subglottic Narrowing
HPIV infection of the larynx, trachea, and subglottic airway produces inflammatory edema that narrows the relatively small pediatric subglottis, causing the inspiratory stridor and barking cough of croup (laryngotracheobronchitis). HPIV-1 is the most frequent viral cause of croup; HPIV-2 also causes croup, while HPIV-4 is comparatively more associated with lower respiratory tract involvement.
inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
larynx UBERON:0001737 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in larynx (UBERON:0001737). UBERON:0001737 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (1 reference)
PMID:38900074 SUPPORT Human Clinical
"Compared with the other serotypes, croup was significantly more common in PIV-1 and lower respiratory tract infection was significantly more common in PIV-4."
Pediatric cohort data showing croup is significantly more common with HPIV-1 and lower respiratory tract infection with HPIV-4. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Parainfluenza Virus Infection Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

6
Immune 1
Bronchiolitis HP:0011950 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bronchiolitis (HP:0011950). HP:0011950 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12692097 SUPPORT Other
"HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly."
Supports lower respiratory tract involvement (including bronchiolitis) as a manifestation of HPIV infection. Evidence source is OTHER as this is a review article.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Respiratory 4
Croup Barking cough HP:0033121 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Croup (barking cough), annotated with Barking cough (HP:0033121). HP:0033121 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38900074 SUPPORT Human Clinical
"Compared with the other serotypes, croup was significantly more common in PIV-1 and lower respiratory tract infection was significantly more common in PIV-4."
Supports croup as a characteristic, serotype-associated manifestation of parainfluenza (most common with HPIV-1). Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
Stridor HP:0010307 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Stridor (HP:0010307). HP:0010307 is a phenotype from the Human Phenotype Ontology.
Cough HP:0012735 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cough (HP:0012735). HP:0012735 is a phenotype from the Human Phenotype Ontology.
Rhinorrhea HP:0031417 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Rhinorrhea (HP:0031417). HP:0031417 is a phenotype from the Human Phenotype Ontology.
💊

Medical Actions

2
Supportive Care
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Management of parainfluenza infection is largely supportive (hydration, antipyretics, and respiratory support as needed); no specific antiviral therapy is approved.
Corticosteroid Therapy for Croup
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: dexamethasone CHEBI:41879 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses dexamethasone (CHEBI:41879). CHEBI:41879 is a therapeutic agent from Chemical Entities of Biological Interest.
Croup is treated with corticosteroids (e.g., dexamethasone) to reduce subglottic airway inflammation, with nebulized epinephrine for moderate-to-severe airway obstruction.
Mechanism Target:
INHIBITS Laryngotracheal Inflammation and Subglottic Narrowing — Corticosteroids suppress the laryngotracheal inflammatory edema that narrows the subglottic airway in croup, relieving stridor and respiratory distress.
🦠

Infectious Agent

4
Human respirovirus 1 (HPIV-1)
HPIV-1, the leading viral cause of croup (laryngotracheobronchitis) in young children.
Human parainfluenza virus 1 NCBITaxon:12730 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:38900074 SUPPORT Human Clinical
"Parainfluenza virus (PIV) is widely known as a causative virus of acute respiratory tract infections in children, and 4 serotypes (PIV-1-PIV-4) have been identified."
Establishes the four parainfluenza serotypes as causative agents of acute respiratory infection, of which this entry is HPIV-1.
PMID:38900074 SUPPORT Human Clinical
"Compared with the other serotypes, croup was significantly more common in PIV-1 and lower respiratory tract infection was significantly more common in PIV-4."
A 1490-case pediatric series showing the distinct clinical signature of HPIV-1, supporting it as a separately identified agent.
Human orthorubulavirus 2 (HPIV-2)
HPIV-2, a less frequently detected serotype that also causes croup and upper respiratory illness, occurring at an older median age than the other types.
Human parainfluenza virus 2 NCBITaxon:2560525 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:38900074 SUPPORT Human Clinical
"Of the 1490 cases, 608 were positive for a single PIV serotype: 91 (13.5%) for PIV-1, 54 (4.8%) for PIV-2, 361 (62.1%) for PIV-3 and 102 (19.6%) for PIV-4."
Documents HPIV-2 as one of the four serotypes recovered from children with respiratory illness, and its relative frequency.
Human respirovirus 3 (HPIV-3)
HPIV-3, the most frequently detected serotype and an important cause of bronchiolitis and pneumonia in infancy.
Human parainfluenza virus 3 NCBITaxon:11216 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:38900074 SUPPORT Human Clinical
"Of the 1490 cases, 608 were positive for a single PIV serotype: 91 (13.5%) for PIV-1, 54 (4.8%) for PIV-2, 361 (62.1%) for PIV-3 and 102 (19.6%) for PIV-4."
Documents HPIV-3 as the most commonly detected serotype in a large pediatric series.
PMID:12692097 SUPPORT Other
"HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly."
Supports HPIV-3, with HPIV-1 and HPIV-2, as a major cause of lower respiratory infection across the affected host groups.
Human orthorubulavirus 4 (HPIV-4)
HPIV-4, historically regarded as the mildest serotype but associated with a higher proportion of lower respiratory tract involvement in contemporary pediatric series.
Human parainfluenza virus 4 NCBITaxon:2560526 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:38900074 SUPPORT Human Clinical
"Compared with the other serotypes, croup was significantly more common in PIV-1 and lower respiratory tract infection was significantly more common in PIV-4."
Identifies HPIV-4 as a distinct agent with a lower-respiratory-predominant presentation in children.
↔️

Transmission

2
Large respiratory droplet transmission
Human parainfluenza viruses are acquired by inhalation of large respiratory droplets produced by an infected person, the route shared by the major paramyxovirus and orthomyxovirus respiratory pathogens.
Show evidence (2 references)
PMID:17600390 SUPPORT Other
"The infections are generally acquired by transmission of large respiratory droplets and can be nosocomial in origin with many documented outbreaks on specialised transplant units."
States large respiratory droplets as the usual route for the viral respiratory infections this review covers.
PMID:17600390 SUPPORT Other
"The most common RTI pathogens are influenza viruses, parainfluenza viruses and respiratory syncytial viruses."
Confirms that parainfluenza viruses are among the pathogens to which the droplet-transmission statement in this review applies.
Nosocomial person-to-person transmission
HPIV-3 spreads between hospitalised patients and staff, causing ward outbreaks that are severe in haematology and transplant populations.
Show evidence (1 reference)
PMID:21466639 SUPPORT Human Clinical
"Epidemiological analysis of the outbreak supported the molecular data with nosocomial transmission of the same genetic strain as the cause of the outbreak."
Sequence-confirmed spread of a single HPIV-3 strain across 17 patients and a healthcare worker demonstrates person-to-person transmission.
📊

Related Datasets

1
Immune response of human lung tissue after infection with human parainfluenza virus-3 – canonical pathways and treatment geo:GSE290099
Ex vivo human precision-cut lung slices (PCLS) were infected with human parainfluenza virus 3 (hPIV-3). We used microarry to explore the changes in gene expression between infected and non-infected, same-donor PCLS. We particularly analyzed changes in mRNA and miRNA expression levels linked to inflammation and antiviral immunity.
human MICROARRAY n=31
PMID:41239423
Identified by GEO DataSets index search for Parainfluenza Virus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
{ }

Source YAML

click to show 
name: Parainfluenza Virus Infection
creation_date: "2026-06-28T00:00:00Z"
description: >
  Parainfluenza virus infection is an acute respiratory infection caused by the
  human parainfluenza viruses (HPIV; enveloped, negative-sense single-stranded
  RNA viruses of the family Paramyxoviridae), divided antigenically and
  genetically into types 1 to 4. HPIV-1 to HPIV-3 are major causes of upper and
  lower respiratory tract infection in infants, young children, the
  immunocompromised, the chronically ill, and the elderly. Each type tends to
  cause somewhat distinct illness: HPIV-1 (and HPIV-2) are the leading viral
  causes of croup (laryngotracheobronchitis), while HPIV-3 is an important cause
  of bronchiolitis and pneumonia in infancy, second only to respiratory syncytial
  virus. The virus infects the ciliated respiratory epithelium and elicits an
  innate antiviral/interferon and inflammatory response that drives much of the
  symptomatic illness.
category: Infectious Disease
parents:
- Viral Respiratory Infection
synonyms:
- Human parainfluenza virus infection
- HPIV infection
- Parainfluenza
disease_term:
  preferred_term: parainfluenza infection
  term:
    id: MONDO:0100197
    label: parainfluenza infectious disease
infectious_agent:
- name: Human respirovirus 1 (HPIV-1)
  infectious_agent_term:
    preferred_term: Human parainfluenza virus 1
    term:
      id: NCBITaxon:12730
      label: Human respirovirus 1
  description: >-
    HPIV-1, the leading viral cause of croup (laryngotracheobronchitis) in young
    children.
  evidence:
  - reference: PMID:38900074
    reference_title: "Clinical Characteristics of Pediatric Parainfluenza Virus Infections: A Comparative Analysis of Parainfluenza Virus Serotypes 1-4 From April 2021 to October 2023 in Hokkaido, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Parainfluenza virus (PIV) is widely known as a causative virus of acute
      respiratory tract infections in children, and 4 serotypes (PIV-1-PIV-4) have
      been identified.
    explanation: >-
      Establishes the four parainfluenza serotypes as causative agents of acute
      respiratory infection, of which this entry is HPIV-1.
  - reference: PMID:38900074
    reference_title: "Clinical Characteristics of Pediatric Parainfluenza Virus Infections: A Comparative Analysis of Parainfluenza Virus Serotypes 1-4 From April 2021 to October 2023 in Hokkaido, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with the other serotypes, croup was significantly more common in
      PIV-1 and lower respiratory tract infection was significantly more common in
      PIV-4.
    explanation: >-
      A 1490-case pediatric series showing the distinct clinical signature of
      HPIV-1, supporting it as a separately identified agent.
- name: Human orthorubulavirus 2 (HPIV-2)
  infectious_agent_term:
    preferred_term: Human parainfluenza virus 2
    term:
      id: NCBITaxon:2560525
      label: Human orthorubulavirus 2
  description: >-
    HPIV-2, a less frequently detected serotype that also causes croup and upper
    respiratory illness, occurring at an older median age than the other types.
  evidence:
  - reference: PMID:38900074
    reference_title: "Clinical Characteristics of Pediatric Parainfluenza Virus Infections: A Comparative Analysis of Parainfluenza Virus Serotypes 1-4 From April 2021 to October 2023 in Hokkaido, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the 1490 cases, 608 were positive for a single PIV serotype: 91 (13.5%)
      for PIV-1, 54 (4.8%) for PIV-2, 361 (62.1%) for PIV-3 and 102 (19.6%) for
      PIV-4.
    explanation: >-
      Documents HPIV-2 as one of the four serotypes recovered from children with
      respiratory illness, and its relative frequency.
- name: Human respirovirus 3 (HPIV-3)
  infectious_agent_term:
    preferred_term: Human parainfluenza virus 3
    term:
      id: NCBITaxon:11216
      label: Human respirovirus 3
  description: >-
    HPIV-3, the most frequently detected serotype and an important cause of
    bronchiolitis and pneumonia in infancy.
  evidence:
  - reference: PMID:38900074
    reference_title: "Clinical Characteristics of Pediatric Parainfluenza Virus Infections: A Comparative Analysis of Parainfluenza Virus Serotypes 1-4 From April 2021 to October 2023 in Hokkaido, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the 1490 cases, 608 were positive for a single PIV serotype: 91 (13.5%)
      for PIV-1, 54 (4.8%) for PIV-2, 361 (62.1%) for PIV-3 and 102 (19.6%) for
      PIV-4.
    explanation: >-
      Documents HPIV-3 as the most commonly detected serotype in a large pediatric
      series.
  - reference: PMID:12692097
    reference_title: Parainfluenza viruses.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      HPIV-1 to HPIV-3 are major causes of lower respiratory infections in
      infants, young children, the immunocompromised, the chronically ill, and the
      elderly.
    explanation: >-
      Supports HPIV-3, with HPIV-1 and HPIV-2, as a major cause of lower
      respiratory infection across the affected host groups.
- name: Human orthorubulavirus 4 (HPIV-4)
  infectious_agent_term:
    preferred_term: Human parainfluenza virus 4
    term:
      id: NCBITaxon:2560526
      label: Human orthorubulavirus 4
  description: >-
    HPIV-4, historically regarded as the mildest serotype but associated with a
    higher proportion of lower respiratory tract involvement in contemporary
    pediatric series.
  evidence:
  - reference: PMID:38900074
    reference_title: "Clinical Characteristics of Pediatric Parainfluenza Virus Infections: A Comparative Analysis of Parainfluenza Virus Serotypes 1-4 From April 2021 to October 2023 in Hokkaido, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with the other serotypes, croup was significantly more common in
      PIV-1 and lower respiratory tract infection was significantly more common in
      PIV-4.
    explanation: >-
      Identifies HPIV-4 as a distinct agent with a lower-respiratory-predominant
      presentation in children.
transmission:
- name: Large respiratory droplet transmission
  description: >-
    Human parainfluenza viruses are acquired by inhalation of large respiratory
    droplets produced by an infected person, the route shared by the major
    paramyxovirus and orthomyxovirus respiratory pathogens.
  evidence:
  - reference: PMID:17600390
    reference_title: "Viral respiratory tract infections in transplant patients: epidemiology, recognition and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The infections are generally acquired by transmission of large respiratory
      droplets and can be nosocomial in origin with many documented outbreaks on
      specialised transplant units.
    explanation: >-
      States large respiratory droplets as the usual route for the viral
      respiratory infections this review covers.
  - reference: PMID:17600390
    reference_title: "Viral respiratory tract infections in transplant patients: epidemiology, recognition and management."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The most common RTI pathogens are influenza viruses, parainfluenza viruses
      and respiratory syncytial viruses.
    explanation: >-
      Confirms that parainfluenza viruses are among the pathogens to which the
      droplet-transmission statement in this review applies.
- name: Nosocomial person-to-person transmission
  description: >-
    HPIV-3 spreads between hospitalised patients and staff, causing ward outbreaks
    that are severe in haematology and transplant populations.
  evidence:
  - reference: PMID:21466639
    reference_title: Nosocomial transmission of parainfluenza 3 virus in hematological patients characterized by molecular epidemiology.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Epidemiological analysis of the outbreak supported the molecular data with
      nosocomial transmission of the same genetic strain as the cause of the
      outbreak.
    explanation: >-
      Sequence-confirmed spread of a single HPIV-3 strain across 17 patients and a
      healthcare worker demonstrates person-to-person transmission.
pathophysiology:
- name: Respiratory Epithelial Infection and Innate Immune Response
  conforms_to: "innate_antiviral_interferon_response#Interferon-Stimulated Gene Antiviral State"
  description: >
    HPIV infects the ciliated epithelium of the upper and lower respiratory tract,
    where viral replication is sensed by the host innate immune system and triggers
    a type I/III interferon and inflammatory cytokine response. Much of the
    symptomatic illness reflects this host antiviral and inflammatory response
    together with epithelial injury. HPIV-1 to HPIV-3 are leading causes of lower
    respiratory tract infection in young children and other vulnerable hosts.
  cell_types:
  - preferred_term: respiratory epithelial cell
    term:
      id: CL:0002632
      label: epithelial cell of lower respiratory tract
  - preferred_term: ciliated airway epithelial cell
    term:
      id: CL:0000064
      label: ciliated cell
  biological_processes:
  - preferred_term: viral genome replication
    term:
      id: GO:0019079
      label: viral genome replication
  - preferred_term: defense response to virus
    term:
      id: GO:0051607
      label: defense response to virus
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  locations:
  - preferred_term: respiratory system
    term:
      id: UBERON:0001004
      label: respiratory system
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:12692097
    reference_title: "Parainfluenza viruses."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      HPIV-1 to HPIV-3 are major causes of lower respiratory infections in
      infants, young children, the immunocompromised, the chronically ill, and the
      elderly.
    explanation: >-
      Establishes HPIV-1 to HPIV-3 as major causes of lower respiratory tract
      infection in vulnerable hosts. Evidence source is OTHER as this is a review
      article.
  - reference: PMID:12692097
    reference_title: "Parainfluenza viruses."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      These viruses belong to the Paramyxoviridae family
    explanation: >-
      Identifies HPIV as members of the Paramyxoviridae family. Evidence source is
      OTHER as this is a review article.
  downstream:
  - target: Laryngotracheal Inflammation and Subglottic Narrowing
    description: >-
      In the larynx and subglottic airway, HPIV (especially type 1) infection and
      inflammation narrow the airway, producing croup.

- name: Laryngotracheal Inflammation and Subglottic Narrowing
  description: >
    HPIV infection of the larynx, trachea, and subglottic airway produces
    inflammatory edema that narrows the relatively small pediatric subglottis,
    causing the inspiratory stridor and barking cough of croup
    (laryngotracheobronchitis). HPIV-1 is the most frequent viral cause of croup;
    HPIV-2 also causes croup, while HPIV-4 is comparatively more associated with
    lower respiratory tract involvement.
  locations:
  - preferred_term: larynx
    term:
      id: UBERON:0001737
      label: larynx
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  evidence:
  - reference: PMID:38900074
    reference_title: "Clinical Characteristics of Pediatric Parainfluenza Virus Infections: A Comparative Analysis of Parainfluenza Virus Serotypes 1-4 From April 2021 to October 2023 in Hokkaido, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with the other serotypes, croup was significantly more common in
      PIV-1 and lower respiratory tract infection was significantly more common in
      PIV-4.
    explanation: >-
      Pediatric cohort data showing croup is significantly more common with HPIV-1
      and lower respiratory tract infection with HPIV-4. Evidence source is
      HUMAN_CLINICAL as this is a clinical cohort study.
  downstream: []
phenotypes:
- category: Respiratory
  name: Croup
  description: >
    Laryngotracheobronchitis with the characteristic barking ("seal-like") cough
    and inspiratory stridor, the hallmark presentation of HPIV-1 infection in young
    children.
  phenotype_term:
    preferred_term: Croup (barking cough)
    term:
      id: HP:0033121
      label: Barking cough
  evidence:
  - reference: PMID:38900074
    reference_title: "Clinical Characteristics of Pediatric Parainfluenza Virus Infections: A Comparative Analysis of Parainfluenza Virus Serotypes 1-4 From April 2021 to October 2023 in Hokkaido, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with the other serotypes, croup was significantly more common in
      PIV-1 and lower respiratory tract infection was significantly more common in
      PIV-4.
    explanation: >-
      Supports croup as a characteristic, serotype-associated manifestation of
      parainfluenza (most common with HPIV-1). Evidence source is HUMAN_CLINICAL as
      this is a clinical cohort study.
- category: Respiratory
  name: Stridor
  description: >
    Inspiratory stridor from subglottic airway narrowing during croup.
  phenotype_term:
    preferred_term: Stridor
    term:
      id: HP:0010307
      label: Stridor
- category: Respiratory
  name: Bronchiolitis
  description: >
    Lower respiratory tract involvement with small-airway inflammation, especially
    with HPIV-3 in infants and HPIV-4.
  phenotype_term:
    preferred_term: Bronchiolitis
    term:
      id: HP:0011950
      label: Bronchiolitis
  evidence:
  - reference: PMID:12692097
    reference_title: "Parainfluenza viruses."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      HPIV-1 to HPIV-3 are major causes of lower respiratory infections in
      infants, young children, the immunocompromised, the chronically ill, and the
      elderly.
    explanation: >-
      Supports lower respiratory tract involvement (including bronchiolitis) as a
      manifestation of HPIV infection. Evidence source is OTHER as this is a review
      article.
- category: Respiratory
  name: Cough
  description: >
    Cough is a common manifestation of HPIV respiratory infection.
  phenotype_term:
    preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
- category: Respiratory
  name: Rhinorrhea
  description: >
    Nasal discharge accompanies upper respiratory HPIV infection.
  phenotype_term:
    preferred_term: Rhinorrhea
    term:
      id: HP:0031417
      label: Rhinorrhea
- category: Constitutional
  name: Fever
  description: >
    Fever commonly accompanies acute parainfluenza infection.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
treatments:
- name: Supportive Care
  description: >
    Management of parainfluenza infection is largely supportive (hydration,
    antipyretics, and respiratory support as needed); no specific antiviral therapy
    is approved.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
- name: Corticosteroid Therapy for Croup
  description: >
    Croup is treated with corticosteroids (e.g., dexamethasone) to reduce
    subglottic airway inflammation, with nebulized epinephrine for
    moderate-to-severe airway obstruction.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: dexamethasone
      term:
        id: CHEBI:41879
        label: dexamethasone
  target_mechanisms:
  - target: Laryngotracheal Inflammation and Subglottic Narrowing
    treatment_effect: INHIBITS
    description: >-
      Corticosteroids suppress the laryngotracheal inflammatory edema that narrows
      the subglottic airway in croup, relieving stridor and respiratory distress.
notes: >
  Created as part of the Respiratory Infections project (Intercept-aligned endemic
  respiratory viruses). Conforms to the innate_antiviral_interferon_response
  module via the epithelial innate/interferon response node. The infectious_agent
  (NCBITaxon) and transmission blocks were backfilled under dismech#10115; all four
  HPIV types are carried as separate agents within this single entry.
datasets:
- accession: geo:GSE290099
  title: Immune response of human lung tissue after infection with human parainfluenza virus-3 – canonical pathways and treatment
  description: Ex vivo human precision-cut lung slices (PCLS) were infected with human parainfluenza virus 3 (hPIV-3). We used microarry to explore the changes in gene expression between infected and non-infected, same-donor PCLS. We particularly analyzed changes in mRNA and miRNA expression levels linked to inflammation and antiviral immunity.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: MICROARRAY
  sample_count: 31
  publication: PMID:41239423
  notes: Identified by GEO DataSets index search for Parainfluenza Virus Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.