# Gizem Gören

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> [name=Gizem Gören]

> [time=Sat, May 29 2021 15:45 PM]

**PARAMYXOVIRUSES: [Virology by P. Saravanan, 2019]**
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- from Greek para- “by the side of” and myxa “mucus”
- The family Paramyxoviridae are enveloped negative-banded ssRNA viruses with a diameter of 150-200 nm. It has 2 subfamilies. They are Paramyxovirinae and Pneumovirinae. Paramixovirus is a species of virus belonging to the family paramixoviridae. It has enveloped virions. It has an endogenous RNA polymerase. This is essential for the transcription of the negative sense strand into the positive sense strand. In this way, it can be encoded from RNA.
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# **Paramyxoviruses Family**

- The family Paramyxoviridae consists of three genera: Paramyxovirus, Pneumovirus, and Morbillivirus.
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# **Morphology and Structural Proteins**


- Paramyxovirus virion structure. (A) Negative-contrast electron micrograph of intact measles virus particle (genus Morbillivirus). Scale bar = 100 nm. (B) Schematic diagram of paramyxovirus particle in cross-section.

- Virions have lipid envelopes surrounding the nucleocapsid. This lipid envelope is produced by budding directly from the plasma membrane of the host cell. There are two transmembrane proteins.
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# *Paramyxovirus genome structure*
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# *Structure Proteins*

- **Conserved domain structures of paramyxovirus fusion protein (A) and attachment protein (B)**

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# **Taxonomy**


- Phylogenetic tree of paramyxoviruses
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# **Paramyxovirus Nucleocapsid**


- **Organization of the paramyxovirus nucleocapsid**
- Nucleocapsid proteins for all paramyxoviruses are formed by the helical structure of N proteins that surround viral RNA.

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# **Paramyxovirus Attachment**


- Three activities of paramyxovirus attachment proteins. These first attach the virions to sialic acid-containing receptors on target cell surfaces (HA), then promote the fusion of viral and cellular membranes. Viruses that fail to initiate infection can move away from cell surfaces as a result of the activity of the binding protein neuraminidase (NA). NA activation also facilitates the release of budding progeny virus from infected cell surfaces.

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# **Paramyxovirus Entry**


- The attachment and Fusion envelope glycoproteins. A)Important functional domains. For glycoprotein attachment, the transmembrane domain, cytoplasmic tail, proposed STEM domain, and spherical head are specified. There are F1 and F2 subunits for Fusion glycoprotein. It contains the F2 signal sequence and contains the F1 transmembrane domain, cytoplasmic tail, fusion peptide, heptad repeat a (HRA) and heptad repeat B (HRB). B)Orientation of glycoprotein binding and fusion in virion membrane. F is a typical type 1 membrane glycoprotein with a membrane propagation area and an extracellular n-terminal. There is a disulfide bond connecting the F1 and F2 subunits, and it has been shown. Binding glycoproteins are Type II membrane proteins in which amino (N)-terminus molecules are directed towards the cytoplasm and the carboxy C-terminus of the protein is extracellular.

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# **Paramyxovirus Transcription and Replication**

- **Schematic diagram illustrating a representative paramyxovirus genome and transcription and RNA replication products.**
- The genes represent purple boxes. the gs and ge signals are shown sequentially in white and black boxes. The green arrows show the le and tr promoters at the 3' ends of the genome and antigenome respectively. The genome acts as a template for mRNA and antigenome synthesis, and the antigen as a template for genome RNA synthesis. Black circles symbolize mRNA covers. Gray ovals representing the N protein are used to show that the antigenome is covered.
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# **Paramyxovirus Assembly**


- **Potential models of paramyxovirus assembly: fusion protein shown in purple, attachment protein in magenta, matrix protein in green and the RNP complex in brown**.
- In the first model, fusion and binding proteins interact and are complexly transported to the plasma membrane. In the second model, the fusion protein can bind the matrix protein in the endoplasmic reticulum. The two are transported to the plasma membrane, where they form a nucleation zone for assembly. A third model is proposed regarding the role of the cytoplasmic tail of F in targeting m-RNP to assembly. These models and other studies give insight into the assembly of paramyxovirus.

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# **Viral Life Cycle of Paramyxovirus**


- **In the figure are the components of a paramyxovirus and the viral life cycle. Schematically, the main steps of the life cycle are shown.**

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- **This figure shows the general life cycles of paramyxoviruses**.
- It results in newly synthesized virus particles being collected and released into the extracellular matrix. The infection is initiated by binding of the binding protein to the cell surface receptor. The Viral genome is then released into the cytoplasm for a replication cycle. The newly synthesized viral components translocate to discrete sites at the infected cell plasma membrane where assembly and budding of infectious virus particles occur.
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# **Inhibitory Discovery of Paramyxovirus Polymerases**


- Antiviral drug binds to paramyxovirus polymerases, viral protein complexes essential for viral genome replication and expression of viral proteins. It then inhibits them.

- This compound found is well tolerated and has been observed to make a full recovery from a deadly paramyxovirus infection in animals when administered orally.

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