Paramyxovirus Structure Classification and Medical Importance

Paramyxovirus is any virus belonging to the Paramyxoviridae family. Paramyxoviruses have enveloped virions (or virus particles) with diameters ranging from 150 to 200 nm (1 nm = 109 metres). The nucleocapsid that consists of a protein shell (or the capsid) and has the viral nucleic acids has helical symmetry.

Paramyxovirus Virus Genome and Paramyxovirus Causes

The paramyxovirus virus genome consists of a single strand of negative-sense non-segmented RNA (ribonucleic acid). An endogenous RNA polymerase is present and is necessary for the transcription of the negative-sense strand as well into the positive-sense strand, thereby enabling the proteins to be encoded from RNA. The lipoprotein envelope has two glycoprotein spikes designated from the fusion factor (F) and hemagglutinin-neuraminidase (HN).

Subfamilies

Paramyxoviridae has 2 subfamilies called Pneumovirinae and Paramyxovirinae, each of which has multiple genera. Rubulavirus, which includes several types of mumps viruses and human parainfluenza viruses, is an example of Paramyxoviridae genera; Avulavirus, which contains the agents that cause distemper in dogs and cats, measles in humans, and rinderpest in cattle; and Morbillivirus, which contains the agents that cause distemper in dogs and cats, measles in humans, and rinderpest in cattle. The subfamily Pneumovirinae is made up of Pneumovirus species that cause serious respiratory syncytial virus disease in human infants.

Structure

Virions are enveloped and may be pleomorphic or spherical and capable of producing filamentous virions. The diameter is up to 150 nm. Genomes are linear and around 15kb in length. Fusion proteins and the attachment proteins appear as spikes on the virion surface. Matrix proteins present inside the envelope stabilize the structure of the virus. The nucleocapsid core is composed of nucleocapsid proteins, genomic RNA, polymerase, and phosphoproteins proteins.

Genome

The genome is negative-sense RNA, non-segmented, 15–19 kilobases in length, and contains 6 - 10 genes. Extracistronic (noncoding) regions are:

• A 5’ trailer sequence, which is 50–161 nucleotides long

• A 3’ leader sequence, which is 50 nucleotides in length that acts as a transcriptional promoter.

• Intergenomic regions between every gene, which are 3 nucleotides long for morbilliviruses, henipaviruses, and respiro viruses, and variable-length (one-56 nucleotides) for rubella viruses.

Each gene has transcription start or stops signals at the beginning and end, which are transcribed as part of the gene.

Gene sequence within the genome is conserved across the paramyxovirus family because of a phenomenon called transcriptional polarity, where the genes closest to the 3’ end of the genome are transcribed in a greater abundance compared to those towards the 5’ end. This is a result of the genome structure. After every gene is transcribed, the RNA-dependent RNA polymerase pauses to release new mRNA when it encounters the intergenic sequence.

A chance exists that it will dissociate from the RNA genome when the RNA polymerase is paused. It must re-enter the genome at the leader sequence if it dissociates, rather than continuing to transcribe the genome’s length. The result is, the further downstream genes are from the leader sequence, the less they will be transcribed by the RNA polymerase.

Evidence for the single promoter model was verified when viruses were exposed to UV light. UV radiation may cause dimerization of RNA that prevents the transcription by RNA polymerase. If the viral genome follows the multiple promoter model, the level of inhibition of the transcription should correlate with the RNA gene length. However, the genome was best described by the single promoter model. The degree of transcription inhibition was proportional to the distance from the leader sequence when the paramyxovirus genome was exposed to UV light. It means, the further the gene is from the sequence of leaders, the greater the chance of RNA dimerization, inhibiting the RNA polymerase.

The virus takes advantage of the single promoter model by storing its genes in the order in which proteins are necessary for paramyxovirus infection. For example, nucleocapsid protein (N), which is one of the paramyxovirus examples is required in greater amounts than RNA polymerase (L).

Proteins

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The above figure is the illustration of Paramyxoviridae virus virion. 

• N – the nucleocapsid protein binds to genomic RNA (one molecule per hexamer) and prevents it from being digested by nucleases.

• P – the phosphoprotein binds to both L and N proteins and forms the part of the RNA polymerase complex.

• M – the matrix protein assembles between the nucleocapsid and envelope core; it organizes and maintains the structure of the virion.

• F – the fusion protein projects as a trimer from the envelope surface and mediates the entry of the cell by inducing fusion between the cell membrane and the viral envelope by class I fusion. The defining characteristics of the members of the family Paramyxoviridae are the need for a neutral pH for fusogenic activity.

• H/HN/G – The cell attachment proteins extend from the spike's surface and span viral envelopes.

• L – the large protein is given as the catalytic subunit of RNA-dependent RNA polymerase (RDRP).

• Accessory Proteins – it is a mechanism called RNA editing that allows multiple proteins to be produced from the P-gene.