Togaviruses: Symptoms and Structure

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Which enzyme catalyzes the synthesis of full-length antigenome RNA in the cytoplasm of the host cell?

nsP4: RNA polymerase

What conformational changes occur in the E1/E2 heterodimer once inside the endosome?

pH drop leads to conformational changes in E1/E2 heterodimer, leading to fusion after exposure of fusion domain

What is the fate of the RNA genome once it is inside the cytoplasm of the host cell?

It is released to be translated

What is the function of nsP1 in the cytoplasm of the host cell?

nsP1 functions as an RNA capping enzyme

How are the structural proteins post-translationally cleaved in the host cell?

Cleaved by host signal peptidase and furin protease

Which cellular location is responsible for palmitoylating the structural proteins?

The Golgi apparatus

What is the function of the E3 protein in the context of the virus?

Amino-terminal part of PE2 containing the signal sequence

How does the virus exit the host cell?

The virus exits the cell by budding

What are the symptoms of togavirus infection in animals and humans?

Symptoms range from rashes, high fever to joint pain and encephalitis.

What is the size and structure of the togavirus envelope?

Spherical enveloped particle with a fringe of projections (spikes) ~70nm in diameter. It consists of 240 heterodimers of glycoproteins E1 and E2.

Describe the genetic makeup of the togavirus RNA genome.

The togavirus RNA genome is a linear ‘+’ sense ssRNA genome of approximately 9.7-11.8kb. It has both a 5’ methylated cap and a 3’ poly(A) tail (~70nt).

How does the E glycoprotein of the togavirus bind to cellular receptors?

The E glycoprotein binds to cellular receptors, leading to receptor-mediated endocytosis, for example, via the laminin receptor, through clathrin-coated vesicles.

Several togaviruses cause disease in animals and humans> symptoms range from rashes, high fever to joint pain and ______

encephalitis

Envelope: 240 heterodimers of glycoproteins E1 and E2, capsid: 240 copies of ______ proteins

capsid

Linear ‘+’ sense ssRNA genome ~9.7-11.8kb and has both 5’ methylated cap and a 3’ ______ tail (~70nt)

poly(A)

E glycoprotein binds to cellular receptors> receptor mediated endocytosis (e.g. ______ receptor) via clathrin coated vesicles

laminin

Once in endosome, pH drop leads to conformational changes in E1/E2 heterodimer> leads to fusion after exposure of fusion domain - Fusion of endosome membrane with viral envelope> release of ______ Section 3.3 - Once inside the cytoplasm, RNA genome is released to be translated (may interact with cellular proteins to release the genome  nsP1: RNA capping enzyme:.  nsP2: cysteines proteinase, RNA helicase.  nsP4: RNA polymerase  These partly cleaved non-structural proteins catalyse synthesis of full-length antigenome RNA BLUE: If the RNA polymerase stopped at the codon, it would make protein123. If it go through, it would make protein 123+4; P4 is an RNA dependent RNA polymerase - Structural proteins are cleaved during translation and directed to different cellular locations - A polyprotein is generated and post-translationally cleaved by host signal peptidase and furin protease - Structural proteins are palmitoylated (adding fatt acids) in the Golgi - A capsid protein domain binds to the packaging signal on the genome RNA PE2: Precurosr to E2, palmitoylated and glycosylated Capsid: forms ______ E3: Amino-terminal part of PE2 containing the signal sequence E2: Carboxy-terminal part of PE2, a component of virus envelope projections 6K: membrane associated; palmitoylated E1: Component of virion envelope projections; type I transmembrane glycoproteins Section 3.4 - Capsid proteins interact with the cytoplasmic tails of envelope proteins studding the plasma membrane - Virus exits cell by budding.

nucleocapsid

NsP1 is an RNA ______ enzyme

capping

NsP2 has activities as cysteine proteinase and RNA ______

helicase

NsP4 is an RNA ______

polymerase

If the RNA polymerase stopped at the codon, it would make protein123. If it go through, it would make protein 123+4; P4 is an RNA dependent RNA ______

polymerase

A polyprotein is generated and post-translationally cleaved by host signal peptidase and ______ protease

furin

The structural proteins are ______ in the Golgi

palmitoylated

PE2 is a precursor to E2, which is ______ and glycosylated

palmitoylated

Virus exits cell by ______

budding

Learn about the symptoms and structure of togaviruses, which cause disease in animals and humans. Understand how the virus spreads through mosquitoes and the unique features of its spherical enveloped particle.

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