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<unk> . These include: Virus GenBank acronym NCBI taxonomy Notes<unk><unk>  virus type 1 HPIV-1 12730 Most common cause of croup<unk><unk>  virus type 2 HPIV-2 11212 Causes croup and other upper and lower respiratory tract illnesses<unk><unk>  virus type 3 HPIV-3 11216 Associated with bronchiolitis and pneumonia<unk><unk>  virus type 4 HPIV-4 11203 Includes subtypes 4a and 4b HPIVs belong to two genera: Respirovirus (HPIV-1 & HPIV-3) and Rubulavirus (HPIV-2 & HPIV-4). Viral structure and organisation HPIVs are characterised by producing enveloped virions and containing single stranded negative sense RNA. Non-infectious virions have also been reported to contain RNA with positive polarity. HPIV genomes are about 15,000 nucleotides in length and encode six key structural proteins. 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). 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<unk>  (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). 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. 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<unk>  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. 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). The pathogenicity of HPIVs is mutually dependent on the<unk>  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<unk> . However, infections have been induced in other animals (both under natural and experimental situations), although these were always asymptomatic.
Human parainfluenza viruses
Influenza A virus
Influenza B virus
Influenza D virus
Respiratory syncytial virus
Rhinovirus
Novel coronavirus
Chinese coronavirus