Human parainfluenza viruses

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.

The viruses can be detected via cell

culture, immunofluorescent microscopy,
and PCR.[4] HPIVs remain the second main
cause of hospitalisation in children under 5
years of age suffering from a respiratory
illness (only Human orthopneumovirus causes
more respiratory hospitalisations for this age
group).

Classification
The first HPIV was discovered in the late 1950s.
The taxonomic division is broadly based
on antigenic and genetic characteristics,
forming four major serotypes or clades, which
today are considered distinct viruses.[6] These
include:

VirusGenBank acronymNCBI
taxonomyNotesHuman parainfluenza virus
type 1HPIV-112730Most common cause
of croupHuman parainfluenza virus type
2HPIV-211212Causes croup and other upper
and lower respiratory tract illnessesHuman
parainfluenza virus type
3HPIV-311216Associated
with bronchiolitis and pneumoniaHuman
parainfluenza virus type 4HPIV-411203Includes
subtypes 4a and 4b

HPIVs belong to two

genera: Respirovirus (HPIV-1 & HPIV-3)
and Rubulavirus (HPIV-2 & HPIV-4).[3]

Viral structure and organisation

hPIVs are characterised by producing
enveloped virions and containing single
stranded negative
sense RNA.[3] Non-infectious virions have also
been reported to contain RNA with positive
polarity.[3] HPIV genomes are about
15,000 nucleotides in length and encode six
key structural 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
proteinLocationFunctionHemagglutinin-neura
minidase (HN)EnvelopeAttachment and cell
entryFusion Protein (F)EnvelopeFusion and
cell entryMatrix Protein (M)Within the
envelopeAssemblyNucleoprotein (NP)Nucleoca
psidForms a complex with the RNA
genomePhosphoprotein (P)NucleocapsidForm
s as part of RNA polymerase complexLarge
Protein (L)NucleocapsidForms 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 this rule have
been found and its exact advantages are not
fully understood.

Electrophoresis has shown that the molecular

weight (MW) 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 lipid
membrane. Viral RNA (vRNA) is initially
associated with nucleoprotein (NP),
phosphoprotein (P) and the large protein (L).
The hemagglutinin–neuraminidase (HN) is
involved with viral attachment and thus
hemadsorption and hemagglutination.
Furthermore, the fusion (F) protein is important
in aiding the fusion of the host and viral
cellular membranes, eventually
forming syncytia.[10]

Initially the F protein is in an inactive form (F0)

but can be cleaved by proteolysis to form its
active form, F1 and F2, linked by di-sulphide
bonds. Once complete, this is followed by the
HPIV nucleocapsid entering the cytoplasm of
the cell. Subsequently, genomic transcription
occurs using the viruses own 'viral
RNA-dependent RNA polymerase' (L protein).
The cell's own ribosomes are then tasked
with translation, forming the viral proteins from
the viral 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 positive-sense
RNA (intermediate step, necessary for
producing progeny), and
finally, negative-sense RNA is formed which is
then associated with the nucleoprotein. This
may then be either packaged and released
from the cell by budding or used for
subsequent rounds of transcription and
replication.

The observable and morphological changes

that can be seen in infected cells include the
enlargement of the cytoplasm,
decreased 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.

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.

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References

^ "Virus Taxonomy: 2018

Release" (html). International Committee on
Taxonomy of Viruses (ICTV). October 2018.
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Reference.MD. Retrieved 21
March2012.^ Vulliémoz, D; Roux, L (May
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01. PMC 114204. PMID 11312321.^ Henrickson,
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MC 153148. PMID 12692097.^ a b Moscona, A
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