Human parainfluenza viruses

Source: Wikipedia, the free encyclopedia.
(Redirected from
Parainfluenza virus 3, bovine
)
Human parainfluenza viruses
Transmission electron micrograph of a parainfluenza virus. Two intact particles and free filamentous nucleocapsid
nucleocapsid
Scientific classificationEdit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum:
Negarnaviricota
Class: Monjiviricetes
Order: Mononegavirales
Family: Paramyxoviridae
Groups included
  • Respirovirus (part)
    • Human respirovirus 1
       (formerly Human parainfluenza virus 1)
    • Human respirovirus 3
       (formerly Human parainfluenza virus 3)
  • Rubulavirus
     (part)
Cladistically included but traditionally excluded taxa

Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a paraphyletic group of four distinct single-stranded RNA viruses belonging to the Paramyxoviridae family. These viruses are closely associated with both human and veterinary disease.[2] Virions are approximately 150–250 nm in size and contain negative sense RNA with a genome encompassing about 15,000 nucleotides.[3]

Fusion glycoprotein trimer, Human parainfluenza virus 3 (HPIV3).

The viruses can be detected via

respiratory illness (only respiratory syncytial virus (RSV) causes more respiratory hospitalisations for this age group).[5]

Classification

The first HPIV was discovered in the late 1950s. The taxonomic division is broadly based on

serotypes or clades, which today are considered distinct viruses.[6]
These include:

Virus GenBank acronym NCBI taxonomy Notes
Human parainfluenza virus type 1 HPIV-1 12730 Most common cause of croup
Human parainfluenza virus type 2 HPIV-2 11212 Causes croup and other upper and lower respiratory tract illnesses
Human parainfluenza virus type 3 HPIV-3 11216 Associated with bronchiolitis and pneumonia
Human parainfluenza virus type 4 HPIV-4 11203 Includes subtypes 4a and 4b

HPIVs belong to two genera:

Rubulavirus (HPIV-2 & HPIV-4).[3]

Viral structure and organisation

HPIVs are characterised by producing enveloped virions and containing single stranded negative sense

proteins.[3]

The structural gene sequence of HPIVs is as follows: 3′-NP-P-M-F-HN-L-5′ (the protein prefixes and further details are outlined in the table below).[7]

Structural protein Location Function
Hemagglutinin-neuraminidase (HN) Envelope Attachment and cell entry
Fusion Protein (F) Envelope Fusion and cell entry
Matrix Protein (M) Within the envelope Assembly
Nucleoprotein (NP)
Nucleocapsid
 Forms a complex with the
RNA genome
Phosphoprotein (P)
Nucleocapsid
 Forms as part of RNA polymerase complex
Large Protein (L)
Nucleocapsid
 Forms as part of RNA polymerase complex

With the advent of reverse genetics, it has been found that the most efficient human parainfluenza viruses (in terms of replication and transcription) have a genome nucleotide total that is divisible by the number 6. This has led to the "rule of six" being coined. Exceptions to the rule have been found, and its exact advantages are not fully understood.[8]

molecular weight of the proteins for the four HPIVs are similar (with the exception of the phosphoprotein, which shows significant variation).[3][9]

Viral entry and replication

Viral replication is initiated only after successful entry into a cell by attachment and fusion between the virus and the host cell

syncytia.[10]

Initially the F protein is in an inactive form (F0) but can be cleaved by

mRNA.[10]

Towards the end of the process, (after the formation of the viral proteins) the replication of the viral genome occurs. Initially, this occurs with the formation of a

transcription and replication.[11]

The observable and morphological changes that can be seen in infected cells include the enlargement of the

mitotic activity and 'focal rounding', with the potential formation of multi-nucleate cells (syncytia).[12]

The

pathogenicity of HPIVs is mutually dependent on the viruses having the correct accessory proteins that are able to elicit anti-interferon properties. This is a major factor in the clinical significance of disease.[11]

Host range

The main host remains the human. However, infections have been induced in other animals (both under natural and experimental situations), although these were always asymptomatic.[13]

Clinical significance

It is estimated that there are 5 million children with

Upper respiratory infections (URI) are also important in the context of HPIV, however, they are caused to a lesser extent by the virus.[16] The highest rates of serious HPIV illnesses occur among young children, and surveys have shown that about 75% of children aged 5 or older have antibodies to HPIV-1.[citation needed
]

For infants and young children, it has been estimated that about 25% will develop "clinically significant disease".[17]

Repeated infection throughout the life of the host is not uncommon and symptoms of later breakouts include

upper respiratory tract illness, such as cold and a sore throat.[3] The incubation period for all four serotypes is 1 to 7 days.[18] In immunosuppressed people, parainfluenza virus infections can cause severe pneumonia, which can be fatal.[19]

HPIV-1 and HPIV-2 have been demonstrated to be the principal causative agent behind

laryngotracheobronchitis), which is a viral disease of the upper airway and is mainly problematic in children aged 6–48 months of age.[20][21] Biennial epidemics starting in autumn are associated with both HPIV-1 and -2; however, HPIV-2 can also have yearly outbreaks.[14] Additionally, HPIV-1 tends to cause biennial outbreaks of croup in the fall. In the United States, large peaks have presently been occurring during odd-numbered years.[citation needed
]

HPIV-3 has been closely associated with bronchiolitis and pneumonia, and principally targets those aged <1 year.[22]

HPIV-4 remains infrequently detected. It is now believed to be more common than previously thought but less likely to cause severe disease. By the age of 10, the majority of children are seropositive for HPIV-4 infection—this may be indicative of a large proportion of asymptomatic or mild infections.[3]

Those with compromised immunity have a higher risk of infection and mortality and may fall ill with more extreme forms of LRI.

febrile seizures.[23] HPIV-4b has the strongest association (up to 62%)[vague] followed by HPIV-3 and -1.[3]

HPIVs have also been linked with rare cases of viral meningitis[24] and Guillain–Barré syndrome.[12]

HPIVs are spread from person to person (i.e., horizontal transmission) by contact with infected secretions in respiratory droplets or contaminated surfaces or objects. Infection can occur when infectious material contacts the mucous membranes of the eyes, mouth, or nose, and possibly through the inhalation of droplets generated by a sneeze or cough. HPIVs can remain infectious in airborne droplets for over an hour.[citation needed]

Airway inflammation

The inflammation of the airway is a common attribute of HPIV infection. It is believed to occur due to the large scale upregulation of

chemokines and inflammatory proteins are also believed to be associated with the common symptoms of HPIV infection.[12]

Recent evidence suggests that the virus-specific antibody

trachea that are believed to cause croup.[12][25]

Immunology

The body's primary defense against HPIV infection is adaptive immunity involving both humoral and cellular immunity. With humoral immunity, antibodies that bind to the surface viral proteins HN and F protect against later infection.[26] Patients with defective cell-mediated immunity also experience more severe infection, suggesting that T cells are important in clearing infection.[12]

Diagnosis

Diagnosis can be made in several ways, encompassing a range of multi-faceted techniques:[4]

Because of the similarity in terms of the antigenic profile between the viruses,

serotypes.[3]

Morbidity and mortality

Mortality caused by HPIVs in developed regions of the world remains rare. Where mortality has occurred, it is principally in the three core risk groups (very young, elderly and

immuno-compromised). Long-term changes can however be associated with airway remodeling and are believed to be a significant cause of morbidity.[27] The exact associations between HPIVs and diseases such as chronic obstructive pulmonary disease (COPD) are still being investigated.[28]

In developing regions of the world, preschool children remain the highest mortality risk group. Mortality may be a consequence of primary viral infection or secondary problems, such as bacterial infection. Predispositions, such as malnutrition and other deficiencies, may further elevate the chances of mortality associated with infection.[12]

Overall, LRIs cause approximately 25–30% of total deaths in preschool children in the developing world. HPIVs are believed to be associated with 10% of all LRI cases, thus remaining a significant cause of mortality.[12]

Risk factors

Numerous factors have been suggested and linked to a higher risk of acquiring the infection, inclusive of

environmental pollution and overcrowding.[29]

Prevention

Despite decades of research, no

vaccines currently exist.[30]

phase I trials. HPIV-1 and -2 vaccine candidates remain less advanced.[17]

Vaccine techniques which have been used against HPIVs are not limited to intranasal forms, but also viruses attenuated by cold passage, host range attenuation, chimeric construct vaccines and also introducing mutations with the help of reverse genetics to achieve attenuation.[31]

Maternal

antibodies may offer some degree of protection against HPIVs during the early stages of life via the colostrum in breast milk.[32]

Medication

immuno-compromised, despite the lack of conclusive evidence for its benefit.[12] Protein inhibitors and novel forms of medication have also been proposed to relieve the symptoms of infection.[13]

Furthermore,

antibiotics may be used if a secondary bacterial infection develops. Corticosteroid treatment and nebulizers are also a first line choice against croup if breathing difficulties ensue.[12]

Interactions with the environment

Parainfluenza viruses last only a few hours in the environment and are inactivated by soap and water. Furthermore, the virus can also be easily destroyed using common hygiene techniques and detergents, disinfectants and antiseptics.[4]

Environmental factors which are important for HPIV survival are pH, humidity, temperature and the medium within which the virus is found. The optimal pH is around the physiologic pH values (7.4 to 8.0), whilst at high temperatures (above 37 °C) and low humidity, infectivity reduces.[33]

The majority of transmission has been linked to close contact, especially in

aerosols, large droplets and also fomites (contaminated surfaces).[34]

The exact infectious dose remains unknown.[13]

Economic burden

In economically disadvantaged regions of the world, HPIV infection can be measured in terms of mortality. In the developed world where mortality remains rare, the economic costs of the infection can be estimated. Estimates from the US are suggestive of a cost (based on extrapolation) in the region of $200 million per annum.[3]

References

  1. ^ "Virus Taxonomy: 2018 Release". International Committee on Taxonomy of Viruses (ICTV). October 2018. Retrieved 25 January 2019.
  2. PMID 8055470
    .
  3. ^
    PMID 12692097
    .
  4. ^ a b c "Human Parainfluenza Viruses". Centers for Disease Control and Prevention (2011). Archived from the original on 20 March 2012. Retrieved 21 March 2012.
  5. PMID 21859271
    .
  6. PMID 21413341
    . Retrieved 2009-03-15.
  7. ^ Hunt, Dr. Margaret. "PARAINFLUENZA, RESPIRATORY SYNCYTIAL AND ADENO VIRUSES". Reference.MD. Retrieved 21 March 2012.
  8. PMID 11312321
    .
  9. PMID 12692097
    .
  10. ^
    PMID 16007245
    .
  11. ^
    ISBN 978-0470016176. {{cite book}}: |journal= ignored (help
    )
  12. ^ a b c d e f g h i j "Parainfluenza Virus: Epidemiology". eMedicine. Retrieved 21 March 2012.
  13. ^ a b c d "HUMAN PARAINFLUENZA VIRUS". Public Health Agency of Canada. 2011-04-19. Retrieved 21 March 2012.
  14. ^
    PMID 8075269
    .
  15. PMID 3009769
    .
  16. ^ "Acute Respiratory Infections". WHO. Archived from the original on March 24, 2006. Retrieved 21 March 2012.
  17. ^
    S2CID 41967381
    .
  18. ^ "General information: human parainfluenza viruses". Health Protection Agency. 27 August 2008. Retrieved 21 March 2012.
  19. PMID 8747776
    .
  20. ^ "CDC - Human Parainfluenza Viruses: Common cold and croup". Archived from the original on 2009-03-03. Retrieved 2009-03-15.
  21. ^ "Croup Background". Medscape Reference. Retrieved 21 March 2012.
  22. ^ "Parainfluenza Virus Review". Medscape. Retrieved 21 March 2012.
  23. ^ Stephen B Greenberg; Robert L Atmar. "Parainfluenza Viruses—New Epidemiology and Vaccine Developments". Touch Infectious Disease. Retrieved 21 March 2012.
  24. S2CID 25043753
    .
  25. ^ "Human Parainfluenza Viruses (HPIV) and Other Parainfluenza Viruses: Background, Pathophysiology, Etiology". 17 October 2021. Retrieved 18 March 2023.
  26. PMID 27486735
    .
  27. PMID 21983132
    .
  28. PMID 15845430
    .
  29. PMID 1862276
    .
  30. PMID 18820572
    .
  31. ^ "Parainfluenza Viruses". eLS. Retrieved 21 March 2012.
  32. ^ "Definition of Human parainfluenza virus". MedicineNet. Archived from the original on 5 January 2012. Retrieved 21 March 2012.
  33. PMID 14245166
    .
  34. ^ "Common Cold, Croup and Human Parainfluenza Viruses: Symptoms and Prevention". NewsFlu. Retrieved 21 March 2012.

Further reading

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Human_parainfluenza_viruses&oldid=1215531774"