Life Cycle of the Dengue Fever Virus — HHMI BioInteractive Video

Summary

The dengue virus, an RNA virus, infects immune cells by binding to receptors and entering via endocytosis. Its genome is translated into proteins, initiating replication within the host's cells. The virus matures, assembling new particles that bud off and travel to the cell surface, ready to infect other cells.

Takeaways

• 🦠 Dengue virus is an RNA virus with an outer lipid bilayer envelope and envelope proteins.
• 🔒 The virus targets immune cells and uses two key cell surface receptor molecules for infection: the cognate receptor and the Fc receptor.
• 🔗 The envelope protein of the virus binds to the cognate receptor, initiating receptor-mediated endocytosis.
• 🌡️ The lowered pH within the endosome triggers a conformational change in the envelope proteins, forming spike-like structures.
• 💉 The hydrophobic tips of the spikes penetrate the endosome's membrane, leading to the release of the capsid into the cytoplasm.
• 🧬 The viral RNA is a positive-sense strand, which can be directly translated into proteins by the host cell's machinery.
• 🔄 The viral RNA forms a circular structure, enabling it to be used as a template for both negative-sense and positive-sense RNA synthesis.
• 🛠️ Viral proteins, including a protease enzyme, are activated and aggregate to form the RNA replication complex.
• 🔗 The viral genome is translated as a single poly-protein chain, which is then cleaved into functional proteins.
• 🌐 New virus particles assemble with envelope proteins and capsid proteins, with viral RNA packaged inside, eventually maturing and being released to infect other cells.

Q & A

What type of virus is the Dengue virus?

The Dengue virus is an RNA virus.

What are the two cell surface receptor molecules important in Dengue infection?

The two important cell surface receptor molecules in Dengue infection are the cognate receptor and the Fc receptor.

What phenomenon is the Fc receptor involved in?

The Fc receptor is involved in a phenomenon called antibody-dependent enhancement.

How does the virus enter the host cell?

The virus enters the host cell through a process called receptor-mediated endocytosis, where it is internalized in a structure called the endosome.

What happens to the virus when the pH of the endosome interior is lowered by proton pumps?

When the pH of the endosome interior is lowered, the virus responds by changing the conformation of the envelope proteins to form spike-like structures.

How does the virus's envelope protein facilitate the release of the capsid into the cytoplasm?

The tips of the spikes formed by the envelope proteins are hydrophobic, allowing them to penetrate the endosome's membrane, leading to the fusion of the endosome's and virus's membranes and the release of the capsid into the cytoplasm.

Where does the viral RNA travel to after being released from the capsid?

After being released from the capsid, the viral RNA travels to the rough endoplasmic reticulum.

How is the viral RNA translated into proteins?

The viral RNA, being a positive-sense strand, can be directly translated into proteins. The ends of the RNA form structures that bind to translation initiation proteins, which attach to the ribosome to initiate translation.

What is the role of the protease enzyme in the viral replication process?

In the cytoplasm, a protease enzyme, which is one of the viral proteins, activates all the other proteins in the poly-protein chain, leading to the formation of the RNA replication complex.

How does the virus's RNA form a circle during replication?

The ends of the viral RNA fold up, allowing the RNA to form a circle, which then attaches to the replication complex to start the first round of synthesis.

What is the final step in the maturation of new Dengue viruses before they are released from the cell?

The final step in the maturation of new Dengue viruses is the processing of the pre-membrane protein before the virus reaches the cell surface, which allows the virus to become mature and be released to infect other cells.

Outlines

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🦠 Dengue Virus Lifecycle

The script describes the dengue virus, an RNA virus with a lipid bilayer envelope and envelope proteins. It targets immune cells and uses two cell surface receptors for infection: the cognate receptor for normal infection and the Fc receptor for antibody-dependent enhancement. The virus enters cells via receptor-mediated endocytosis, leading to a series of structural changes that allow it to penetrate the endosome's membrane and release its capsid into the cytoplasm. The viral RNA is then translated into proteins, and the proteins form the RNA replication complex. The RNA is replicated in a circular process, leading to the production of more viral proteins and the assembly of new virus particles. The immature virus particles travel through the Golgi apparatus, mature, and are released to infect other cells.

Keywords

💡Dengue virus

Dengue virus is an RNA virus that causes dengue fever, a mosquito-borne tropical disease. It is characterized by its outer surface being covered with envelope proteins that surround a lipid bilayer envelope. In the video's context, the dengue virus is the main subject, and understanding its structure and life cycle is crucial to grasping the video's theme of how the virus infects and replicates within host cells.

💡Envelope proteins

Envelope proteins are proteins that cover the lipid bilayer of the dengue virus, playing a critical role in the virus's ability to infect host cells. They bind to specific receptors on the host cell surface, initiating the infection process. In the video, the envelope proteins are highlighted as they respond to the lowered pH within the endosome by changing conformation, which is essential for the virus to enter the host cell.

💡Capsid shell

The capsid shell is a protein structure that encloses the viral genome, providing protection and facilitating the delivery of the genetic material into the host cell. In the video, the capsid shell is mentioned as the structure that contains the virus's RNA genome and is released into the host cell's cytoplasm after the virus's entry.

💡Immune cells

Immune cells are a critical component of the body's defense system, including cells like macrophages and dendritic cells. The video explains that the dengue virus targets immune cells, which is an unusual strategy as most viruses target other types of cells. This targeting is significant as it can lead to the virus evading the immune response and causing more severe disease.

💡Receptor-mediated endocytosis

Receptor-mediated endocytosis is a cellular process by which substances are brought into the cell via the formation of an endosome. In the context of the video, the dengue virus's envelope protein binds to a cognate receptor on the host cell, triggering this process, which allows the virus to be internalized within an endosome.

💡Endosome

An endosome is a membrane-bound organelle within the cell that forms during endocytosis. The video describes how the virus is internalized in an endosome, where the proton pumps lower the pH, leading to a conformational change in the virus's envelope proteins, which is a critical step in the infection process.

💡Poly-protein chain

A poly-protein chain refers to a long chain of proteins that are translated from a single mRNA molecule. In the video, it is mentioned that the viral RNA is translated as a single long poly-protein chain, which is then cleaved by viral proteases into individual functional proteins. This is a common strategy among many viruses to economize on genome size and simplify the replication process.

💡RNA replication complex

The RNA replication complex is a group of viral and host proteins that assemble to facilitate the replication of the viral RNA genome. The video explains that the viral proteins aggregate to form this complex, which is essential for the synthesis of new viral RNA strands, a key step in the virus's replication cycle.

💡Golgi apparatus

The Golgi apparatus is an organelle within the cell that is involved in modifying, sorting, and packaging proteins for secretion or delivery to other parts of the cell. In the video, it is mentioned that the immature virus travels through the Golgi apparatus, where it undergoes further processing, including the maturation of the pre-membrane protein, before being released from the cell.

💡Maturation

Maturation in the context of the virus life cycle refers to the process by which newly formed viral particles undergo structural changes to become infectious. The video describes how the dengue virus matures as it travels through the Golgi apparatus, with the processing of the pre-membrane protein being a key aspect of this maturation process.

Highlights

Dengue virus is an RNA virus with envelope proteins and a lipid bilayer envelope.

The virus's RNA genome is contained within a capsid shell.

Dengue virus targets immune cells and uses two cell surface receptor molecules for infection.

The cognate receptor is involved in normal dengue infection.

The FC receptor is involved in antibody-dependent enhancement.

Envelope protein binding to the cognate receptor triggers receptor-mediated endocytosis.

The virus is internalized within an endosome, where proton pumps lower the pH.

Lowered pH causes a conformational change in envelope proteins, forming spike-like structures.

Hydrophobic tips of the spikes penetrate the endosome's membrane.

The capsid is released into the cytoplasm after membrane fusion.

Viral RNA is released and travels to the rough endoplasmic reticulum for translation.

The viral RNA is a positive-sense strand, allowing direct translation into proteins.

The viral genome is translated as a single long poly-protein chain.

Capsid protein is on the cytoplasmic side, while envelope and pre-membrane proteins are in the lumen.

A viral protease enzyme activates other proteins in the poly-protein chain.

Proteins aggregate to form the RNA replication complex.

Viral RNA synthesis involves multiple steps, including circularization and negative-sense strand synthesis.

Many copies of positive-sense RNA are made through repeated cycles of RNA synthesis.

Envelope proteins aggregate in the endoplasmic reticulum, and capsid proteins aggregate on the cytoplasmic side.

Viral RNA binds to the capsid protein and is packaged into a new virus particle.

The virus matures as it travels through the Golgi apparatus and is processed before reaching the cell surface.

New dengue viruses are released from the cell, ready to infect other cells.

Transcripts

>> Dengue virus is an RNA virus.

Its outer surface is covered

with envelope proteins surrounding a lipid

bilayer envelope.

Inside the envelope is a capsid shell

that contains the virus's RNA genome.

Immune cells are targeted by the dengue virus.

There are two cell surface receptor molecules important

in dengue infection.

The cognate receptor is involved in normal infection

and the FC receptor is involved

in a phenomenon called antibody-dependent enhancement.

The virus's envelope protein binds to the cognate receptor

and triggers a cellular process called

receptor-mediated endocytosis.

The virus is internalized in a bubble-like

structure called the endosome.

When endosomes form,

proton pumps lower the pH of the interior.

The virus responds to the lowered pH

by changing the conformation of the envelope proteins

to form spike-like structures.

The tips of the spikes are hydrophobic, which allows them

to penetrate the endosome's membrane.

They bend until the endosome's membrane

and the virus's membrane fuse together

and release the capsid into the cytoplasm.

The capsid breaks apart and releases the viral RNA.

The viral RNA travels to the rough endoplasmic reticulum.

It is a positive-sense strand

and can be directly translated into proteins.

The ends of the RNA form structures that bind

to translation initiation proteins.

The complex attaches to the ribosome

to initiate translation.

The whole viral genome is translated as a single,

long, poly-protein chain.

The capsid protein is on the cytoplasm side

of the endoplasmic reticulum.

The envelope protein and the pre-membrane protein are

in the lumen side and are activated

by the host's peptidase enzyme.

In the cytoplasm, one of the viral proteins,

a protease enzyme, activates all the other proteins

in a poly-protein chain.

These proteins aggregate

to form the RNA replication complex.

The viral RNA is synthesized in multiple steps.

First, the ends of the viral RNA fold up,

and the RNA forms a circle.

The RNA then attaches to the replication complex

to start the first round of synthesis.

Using the virus's positive- sense RNA as the template,

a negative-sense copy is made.

The pair of RNA strands forms a double helix.

The RNA then becomes a circle again.

This time, the negative-sense strand acts as a template

to make a positive-sense strand.

Many copies of the positive-sense RNA are made

by repeated cycles of RNA synthesis.

Some of these strands are translated

to make more viral proteins.

Eventually enough proteins are made to assemble new viruses.

The envelope proteins aggregate in the lumen

of the endoplasmic reticulum

and the capsid proteins aggregate

on the cytoplasmic side.

A viral RNA binds to the capsid protein and is packaged

into a new virus particle as it buds off

into the endoplasmic reticulum.

The virus is still immature.

Its pre-membrane proteins cover the tips

of the envelope proteins

to prevent premature fusion back into the cell.

The virus buds off and travels through the Golgi apparatus

and continues toward the cell's surface.

Before reaching the surface,

the pre-membrane protein is processed,

and the virus becomes mature.

New dengue viruses are released from the cell ready

to infect other cells.