Influenza virus replication Cycle Animation - Medical Microbiology USMLE step 1

Summary

This video explains the process by which the influenza virus infects host cells, from its initial attachment to the host cell through hemagglutinin proteins, to its replication cycle. The virus exploits the cell’s endocytosis mechanism and uses the acidity in the lysosome for uncoating. It describes the 'cap snatching' technique, where the virus hijacks the host's mRNA to replicate itself. The virus assembles new proteins and RNA segments within the cell, eventually forming new viruses that bud from the host's membrane, ready to infect other cells.

Takeaways

• 🦠 The flu is a contagious respiratory infection caused by influenza viruses, which must enter host cells to replicate.
• 🔗 Influenza virus attaches to a host cell using a protein called hemagglutinin, which binds to receptor polysaccharides ending with cyanic acid.
• 🔄 The cell takes up the virus through endocytosis, and the viral particle's acidic environment triggers the uncoating process.
• 💊 Some anti-influenza drugs block the ion channel that allows protons to enter the virus, preventing uncoating.
• 🧬 Hemagglutinin undergoes a structural change, triggering membrane fusion and allowing the viral RNA genome to flow into the cytoplasm.
• 🚪 The viral RNA segments enter the nucleus via nuclear pores, where they are copied into complementary plus strands for protein production.
• 🧢 The virus performs 'cap snatching' by taking a 5' cap from the host's mRNA to start its own viral RNA transcription.
• 🧫 Viral mRNA is translated by the host ribosomes into proteins, including the nucleocapsid and envelope proteins.
• 📦 The newly made RNA segments are packaged into new viruses, which bud off from the cell membrane to infect other cells.
• 🚚 Envelope proteins are transported via vesicles from the endoplasmic reticulum to the Golgi apparatus and then to the plasma membrane.

Q & A

What is the primary cause of the flu?

The flu is caused by influenza viruses, which are contagious respiratory infections.

How does the influenza virus enter a host cell?

The influenza virus enters a host cell by attaching via a protein called hemagglutinin, which binds to a receptor on the host cell's surface, initiating endocytosis.

What role does hemagglutinin play in the infection process?

Hemagglutinin is a viral protein that recognizes and binds to host cell receptors, enabling the virus to enter the cell. It also facilitates membrane fusion during the uncoating process.

How does the virus exploit the host cell's acidity to begin the uncoating process?

The virus uses the acidity inside the endocytic vesicle to disrupt protein-protein interactions, causing matrix proteins to detach from the viral RNA genome, which initiates the uncoating process.

What is cap snatching, and why is it important for the influenza virus?

Cap snatching is a process where the viral RNA polymerase cuts the 5' cap from a host mRNA and uses it to start transcription of viral RNA. This is crucial for making viral mRNA that can be translated by host ribosomes.

Why does the influenza virus need to produce a complementary plus strand of RNA?

The viral RNA genome is a negative-strand RNA, which is non-coding. It must be transcribed into a complementary plus strand before it can be used to make proteins through translation.

How do viral envelope proteins get produced and where are they synthesized?

Viral envelope proteins, such as hemagglutinin, are synthesized by host ribosomes on the endoplasmic reticulum and then transported via vesicles to the Golgi apparatus and plasma membrane.

What happens to the newly synthesized viral RNA and proteins inside the host cell?

The viral RNA segments are combined with RNA polymerase, nucleocapsid proteins, matrix proteins, and packaging proteins. These components are exported from the nucleus and assembled into new virus particles.

How are new virus particles released from the host cell?

New virus particles are assembled and packaged at the host cell's plasma membrane, where they bud off and are released to infect other cells.

What role does the viral ion channel play in the influenza virus infection cycle?

The viral ion channel allows protons to enter the viral particle, which triggers the release of the viral RNA genome by disrupting internal protein interactions, starting the uncoating process.

Outlines

00:00

🦠 Understanding Influenza Virus Infection

This paragraph provides an overview of the influenza virus, a contagious respiratory infection. It explains that the virus needs to enter host cells to replicate, detailing the process which involves several stages such as attachment, entry, viral RNA, protein production, assembly, and release from the host cell.

🔗 Virus Attachment and Entry

The paragraph describes how an influenza virus attaches to a host cell. It focuses on the role of hemagglutinin, a protein in the viral envelope, which binds to host receptors terminating in sialic acid. Following attachment, the virus is taken up by endocytosis into the cell.

🧬 Fusion with Lysosomes and Acidic Activation

This section explains the role of the endocytic vesicle in fusing with a lysosome, which contains digestive enzymes and has an acidic environment. The virus exploits this acidity using an ion channel to allow protons to enter the virus, which disrupts protein-protein interactions and initiates the uncoating process, separating matrix proteins from the viral RNA genome.

💊 Inhibition by Anti-Influenza Drugs

It is noted that certain anti-influenza drugs can block the ion channel that the virus uses to acidify its interior, thereby preventing the uncoating process and hindering the virus's ability to replicate.

🔄 Membrane Fusion and RNA Release

The paragraph details how the acidity also triggers hemagglutinin to change structure and insert into the vesicle membrane, which leads to membrane fusion. This process allows the RNA genome and associated proteins to enter the cytoplasm, completing the uncoating process.

🏗️ RNA Genome Structure and Transport

Here, the structure of the influenza virus's RNA genome is described. The eight RNA segments, which are negative-strand RNAs, are covered with nucleocapsid proteins and attached to viral RNA polymerase. These RNA-protein units enter the nucleus through nuclear pores for replication and transcription.

🧪 Cap Snatching for mRNA Synthesis

The virus synthesizes new viral mRNAs by a method called 'cap snatching', where it cuts off the cap from the host's mRNA molecules and uses it to start the transcription of its own viral RNA. This process is crucial for stabilizing the viral mRNA and ensuring its translation by host ribosomes.

🔬 Viral Protein Synthesis in Cytoplasm

This paragraph covers the translation of viral mRNA into proteins in the cytoplasm by host ribosomes. It highlights how different mRNAs code for various viral proteins, including nucleocapsid and envelope proteins, essential for viral replication and assembly.

🌐 Envelope Protein Production and Transport

It describes the production of envelope proteins, such as hemagglutinin, in the endoplasmic reticulum of the host cell. These proteins are transported via vesicles to the Golgi apparatus and eventually to the plasma membrane.

📦 Packaging of Viral RNA and Proteins

The newly synthesized viral RNA and proteins, including nucleocapsid and matrix proteins, are assembled in the nucleus. The fully formed RNA genome segments and associated proteins are then exported from the nucleus to be packaged into progeny viruses.

🧫 Assembly and Budding of New Viruses

This final paragraph explains the last steps of viral replication, where RNA-protein complexes are packaged into new viruses. These progeny viruses bud from the host cell's plasma membrane, ready to infect new cells and propagate the infection.

Keywords

💡Influenza Virus

The influenza virus is a contagious pathogen that causes respiratory infections. It is central to the video's theme, as the entire transcript explains the virus’s mechanisms for entering host cells, replicating, and causing infection. The virus uses specific proteins to attach to and invade host cells, hijacking their systems to replicate.

💡Hemagglutinin

Hemagglutinin is a protein on the surface of the influenza virus that allows it to attach to host cells. It recognizes and binds to receptor polysaccharides on the cell surface, facilitating viral entry through endocytosis. This protein also undergoes structural changes during the infection process, helping the virus fuse with the host cell membrane.

💡Endocytosis

Endocytosis is the process by which a cell takes in material from its surroundings by engulfing it in a vesicle. In the context of the video, the host cell engulfs the influenza virus through endocytosis after the virus binds to the cell. This allows the virus to enter the cell, where it can begin its replication process.

💡Uncoding Process

The uncoding process refers to the steps the influenza virus takes to release its genetic material inside the host cell. Once inside, the virus uses the acidic environment of the cell to detach proteins from its RNA genome, preparing it for replication. This process is crucial for the virus to begin hijacking the host’s cellular machinery.

💡RNA Genome

The RNA genome of the influenza virus contains its genetic instructions. The virus has eight segments of RNA, each covered with nucleocapsid proteins. These RNA segments are used to replicate the virus and produce the proteins necessary for creating new viral particles. The genome must be copied into a complementary strand before it can be used in protein synthesis.

💡Cap Snatching

Cap snatching is a mechanism by which the influenza virus steals the 5' cap from the host’s mRNA molecules and attaches it to its own viral mRNA. This is necessary for the viral RNA to be recognized by the host’s ribosomes, allowing the virus to produce the proteins it needs for replication. This stealthy act enables the virus to evade the host’s defenses.

💡RNA Polymerase

RNA polymerase is an enzyme complex used by the influenza virus to replicate its RNA. It reads the viral RNA genome and produces complementary RNA strands for protein production. The polymerase is also involved in cap snatching, helping the virus prepare its mRNA for translation in the host’s ribosomes. The viral RNA polymerase is critical for the virus's replication cycle.

💡Nucleocapsid Protein (NP)

Nucleocapsid proteins are proteins that coat the influenza virus’s RNA genome, stabilizing it and protecting it during replication. These proteins also help guide the RNA into the nucleus, where it is transcribed. In the video, the nucleocapsid protein is mentioned as part of the RNA-protein complex that facilitates viral replication inside the host cell.

💡Envelope Proteins

Envelope proteins are viral proteins produced by the host cell’s ribosomes and are embedded in the influenza virus's outer membrane. Hemagglutinin is one of these envelope proteins. They are synthesized on the endoplasmic reticulum and transported to the cell membrane, where they assist in the formation of new viral particles that will bud off from the host cell.

💡Viral Assembly

Viral assembly refers to the process by which newly synthesized viral components—such as RNA segments, nucleocapsid proteins, and envelope proteins—are put together to form new virus particles. In the influenza virus’s life cycle, these components are packaged into progeny viruses that bud off from the host cell membrane to infect new cells.

Highlights

The flu is caused by influenza viruses, which must enter host cells to replicate.

Influenza virus uses hemagglutinin, a protein, to bind to host cell receptors and gain entry via endocytosis.

After entering the cell, the virus exploits the lysosome's acidic environment to begin uncoating.

An ion channel allows protons to enter the virus, disrupting protein-protein interactions and starting the uncoating process.

Anti-influenza drugs can block this ion channel, preventing the virus from exploiting the acidity.

Hemagglutinin undergoes a structural change, allowing it to fuse with the vesicle membrane and complete the uncoating.

The viral RNA genome, along with nucleocapsid proteins, enters the host nucleus to begin replication.

Influenza RNA is non-coding (- strand) and needs to be copied into complementary (+ strand) RNA for protein translation.

The virus performs 'cap snatching,' stealing the 5' cap from host mRNA to start viral RNA transcription.

The viral mRNA receives a poly-A tail for stability before leaving the nucleus for protein translation.

Viral envelope proteins like hemagglutinin are synthesized by the host's endoplasmic reticulum.

Newly made nucleocapsid proteins stabilize viral RNA strands, aiding in the production of additional viral genomes.

Full-length minus strands of RNA are synthesized to serve as the genome segments of new viruses.

Ten different proteins are synthesized from eight RNA segments, and new viral genome segments are exported from the nucleus.

New viruses are assembled and bud off from the host cell membrane, completing the viral replication cycle.

Transcripts

[Music]

the flu is a contagious respiratory

infection caused by influenza viruses

like all viruses influenza must gain

entry into host cells to replicate the

process involves several stages from

attachment and entry to viral RNA and

protein production to assembly and

release from the host cell

an influenza virus attaches to a cell

when hemagglutinin one type of protein

in its viral envelope binds to a host

receptor hemagglutinin recognizes

receptor polysaccharides that terminate

with cyanic acid the cell then takes up

the virus by endocytosis

the endo siddik vesicle then fuses with

a lysosome a lysosome contains digestive

enzymes and an acidic interior and

typically digests contents taken in from

outside the cell

unfortunately for the host the virus

uses the acidity to its advantage an ion

channel allows protons to enter the

virus the acidity inside the viral

particle disrupts protein-protein

interactions causing matrix proteins to

detach from proteins covering the viral

RNA genome this detachment is the

beginning of the un-- coding process

it's interesting to note that one type

of anti influenza drug blocks this ion

channel

the acidity also triggers hemagglutinin

to make a structural change and insert

itself into the vesicle membrane in this

new form hemagglutinin stimulates

membrane fusion the RNA genome and

associated proteins can flow freely away

from the matrix proteins into the

cytoplasm completing the uncoding

process

viii RNA segments of the influenza

genome are covered with nucleo capsid

proteins abbreviated NP and attached to

several other proteins that make up the

viral RNA polymerase these RNA protein

units enter the nucleus via the nuclear

pores

the RNA segments are - strand rnase

meaning that they're non-coding strands

each of the eight segments needs to be

copied into a complementary plus strand

by the viral RNA polymerase before it

can be used for translating proteins

to make a messenger RNA for translation

by host ribosomes the virus needs to add

a structure called a five prime cap at

the beginning of the mRNA transcript the

virus performs a stealthy act known as

cap snatching in which the viral RNA

polymerase cuts off the cap from one of

the host cells own mRNA molecules and

uses the cap to start transcription of

viral RNA the new plus strand viral RNA

gets a poly a tail that aids in mRNA

stability

the new viral mRNA leaves the nucleus

for the cytoplasm where the host cells

ribosomes translate the mRNA in this

example the mRNA codes for the nucleo

capsid protein that will code future

viral RNA molecules

several other mRNAs code for viral

envelope proteins envelope proteins are

made by ribosomes on the host cells

endoplasmic reticulum this particular

mRNA codes for hemagglutinin

back in the nucleus the newly made

nucleo capsid proteins prime and

stabilized viral RNAs as they're being

synthesized into full-length + strands

this time lacking a cap and a poly a

tail newly made RNA polymerase proteins

enter the nucleus and participate in the

production of additional full-length

minus strands that will serve as the RNA

genome segments of new viruses

from these events 10 different types of

proteins are synthesized from 8 RNA

segments and new minus strand RNA genome

segments are produced the RNA genome

segments complex with RNA polymerase

nucleo capsid proteins matrix protein

and packaging proteins are exported from

the nucleus

the envelope proteins made on the

endoplasmic reticulum moved by transport

vesicles from the endoplasmic reticulum

to the Golgi apparatus and finally to

the plasma membrane the RNA protein

complexes are then packaged into progeny

viruses as they bud from the cell

membrane