Paramyxoviridae

Paramyxoviridae (from Greek para- “by the side of” and myxa “mucus”) is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has nine subfamilies that contain 23 genera.

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

Genome

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

A 3' leader sequence, 50 nucleotides in length, which acts as a transcriptional promoter. A 5' trailer sequence, 50 to 161 nucleotides long Intergenomic regions between each gene, which are three nucleotides long for morbilliviruses, respiroviruses, and henipaviruses, and variable length (one to 56 nucleotides) for rubulaviruses. Gene sequence within the genome is conserved across the family due to a phenomenon known as transcriptional polarity (see Mononegavirales) in which genes closest to the 3' end of the genome are transcribed in greater abundance than those towards the 5' end. This is a result of structure of the genome. After each gene is transcribed, the RNA-dependent RNA polymerase pauses to release the new mRNA when it encounters an intergenic sequence. When the RNA polymerase is paused, a chance exists that it will dissociate from the RNA genome. If it dissociates, it must re-enter the genome at the leader sequence, rather than continuing to transcribe the length of the genome. The result is that the further downstream genes are from the leader sequence, the less they will be transcribed by RNA polymerase. Evidence for a single promoter model was verified when viruses were exposed to UV light. UV radiation can cause dimerization of RNA, which prevents transcription by RNA polymerase. If the viral genome follows a multiple promoter model, the level inhibition of transcription should correlate with the length of the RNA gene. However, the genome was best described by a single promoter model. When paramyxovirus genome was exposed to UV light, the level of inhibition of transcription was proportional to the distance from the leader sequence. That is, the further the gene is from the leader sequence, the greater the chance of RNA dimerization inhibiting RNA polymerase. The virus takes advantage of the single promoter model by having its genes arranged in relative order of protein needed for successful infection. For example, nucleocapsid protein (N) is needed in greater amounts than RNA polymerase (L). Viruses in the Paramyxoviridae family are also antigenically stable, meaning that the glycoproteins on the viruses are consistent between different strains of the same type. Two reasons for this phenomenon are posited: The first is that the genome is nonsegmented, thus cannot undergo genetic reassortment. For this process to occur, segments needed as reassortment happen when segments from different strains are mixed together to create a new strain. With no segments, nothing can be mixed with one another, so no antigenic shift occurs. The second reason relates to the idea of antigenic drift. Since RNA-dependent RNA polymerase does not have an error-checking function, many mutations are made when the RNA is processed. These mutations build up and eventually new strains are created. Because of this, paramyxoviruses should not be antigenically stable, but they are. The main hypothesis behind why the viruses are antigenically stable is that each protein and amino acid has an important function. Thus, any mutation would lead to a decrease or total loss of function, which would in turn cause the new virus to be less efficient. These viruses would not be able to survive as long compared to the more virulent strains, and so would die out. Many paramyxovirus genomes follow the "rule of six". The total length of the genome is almost always a multiple of six. This is probably due to the advantage of having all RNA bound by N protein (since N binds hexamers of RNA). If RNA is left exposed, the virus does not replicate efficiently. The gene sequence is:

Nucleocapsid – phosphoprotein – matrix – fusion – attachment – large (polymerase)

Proteins

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