HPIV-1, HPIV-2 and HPIV-3 have been linked with up to a third of these infections. It is estimated that there are 5 million children with lower respiratory infections (LRI) each year in the United States alone. However, infections have been induced in other animals (both under natural and experimental situations), although these were always asymptomatic. This is a major factor in the clinical significance of disease. The pathogenicity of HPIVs is mutually dependent on the viruses having the correct accessory proteins that are able to elicit anti- interferon properties. 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). This may then be either packaged and released from the cell by budding or used for subsequent rounds of transcription and replication. 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. Towards the end of the process, (after the formation of the viral proteins) the replication of the viral genome occurs. The cell's own ribosomes are then tasked with translation, forming the viral proteins from the viral mRNA. Subsequently, genomic transcription occurs using the viruses own 'viral RNA-dependent RNA polymerase' (L protein). Once complete, this is followed by the HPIV nucleocapsid entering the cytoplasm of the cell. Initially the F protein is in an inactive form (F 0) but can be cleaved by proteolysis to form its active form, F 1 and F 2, linked by di-sulphide bonds. Furthermore, the fusion (F) protein is important in aiding the fusion of the host and viral cellular membranes, eventually forming syncytia. The hemagglutinin– neuraminidase (HN) is involved with viral attachment and thus hemadsorption and hemagglutination. Viral RNA ( vRNA) is initially associated with nucleoprotein (NP), phosphoprotein (P) and the large protein (L). Viral replication is initiated only after successful entry into a cell by attachment and fusion between the virus and the host cell lipid membrane. Įlectrophoresis 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). Exceptions to this rule have been found and its exact advantages are not fully understood. This has led to the "rule of six" being coined. 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.
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). HPIV genomes are about 15,000 nucleotides in length and encode six key structural proteins. Non-infectious virions have also been reported to contain RNA with positive polarity. HPIVs are characterised by producing enveloped virions and containing single stranded negative sense RNA. HPIVs belong to two genera: Respirovirus (HPIV-1 & HPIV-3) and Rubulavirus (HPIV-2 & HPIV-4). These include:Ĭauses croup and other upper and lower respiratory tract illnessesĪssociated with bronchiolitis and pneumonia The taxonomic division is broadly based on antigenic and genetic characteristics, forming four major serotypes or clades, which today are considered distinct viruses. The first HPIV was discovered in the late 1950s. Virions are approximately 150–250 nm in size and contain negative sense RNA with a genome encompassing about 15,000 nucleotides. These viruses are closely associated with both human and veterinary disease. HPIVs are a paraphyletic group of four distinct single-stranded RNA viruses belonging to the Paramyxoviridae family. Human parainfluenza viruses ( HPIVs) are the viruses that cause human parainfluenza. Human rubulavirus 4 (formerly Human parainfluenza virus 4) Ĭladistically included but traditionally excluded taxa.Human rubulavirus 2 (formerly Human parainfluenza virus 2).Human respirovirus 3 (formerly Human parainfluenza virus 3).Human respirovirus 1 (formerly Human parainfluenza virus 1).
Two intact particles and free filamentous nucleocapsid Transmission electron micrograph of a parainfluenza virus.