HIV Life Cycle | HHMI BioInteractive Video

Summary

The script explains the life cycle of HIV, a retrovirus that targets T helper cells via CD4 receptors. It details the virus's entry into cells, the conversion of its RNA to DNA by reverse transcriptase, and subsequent integration into the host genome by integrase. The script also covers the production of viral proteins, assembly, and maturation, leading to the release of new virions to infect more cells, perpetuating the infection.

Takeaways

• 🌐 HIV is a retrovirus with an outer envelope and contains two copies of RNA and an enzyme called reverse transcriptase.
• 🔒 The virus infects T helper cells by binding to the CD4 receptor and the chemokine coreceptor (CCR5), leading to a conformational change and membrane fusion.
• 🧬 Reverse transcriptase converts viral RNA into DNA, introducing errors due to its poor proofreading activity.
• 🔄 The single-stranded DNA is further reverse transcribed into double-stranded DNA by the same enzyme.
• 🚀 Integrase carries the double-stranded DNA into the nucleus, where it inserts into the host chromosome, establishing lifelong infection.
• 📜 RNA polymerase transcribes viral RNA, which encodes for various viral proteins that are essential for the virus's structure and function.
• 🛠️ Viral proteins, including the envelope protein, are synthesized and processed through the rough endoplasmic reticulum and Golgi apparatus.
• 🔗 The envelope protein is embedded in the cellular membrane, where it coalesces with other proteins to form a cluster on the cell surface.
• 🌱 Additional viral proteins and RNA are assembled at the cell surface, and the immature virion buds off.
• ⚒️ Protease digests the polyprotein chains, allowing the virus to mature and become infectious, ready to infect other cells.

Q & A

What is a retrovirus and how does HIV fit into this category?

A retrovirus is a type of virus that has an outer envelope and contains two copies of RNA and an enzyme called reverse transcriptase. HIV, or Human Immunodeficiency Virus, is a retrovirus because it shares these characteristics, using reverse transcriptase to convert its RNA into DNA.

How does HIV specifically infect T helper cells?

HIV infects T helper cells by binding to the CD4 molecule, a surface receptor exclusive to these cells. This interaction causes a conformational change that allows a second receptor, the chemokine coreceptor (CCR5), to bind, leading to the fusion of viral and host cell membranes and the injection of viral genetic material.

What is the role of reverse transcriptase in the HIV life cycle?

Reverse transcriptase plays a crucial role in the HIV life cycle by converting viral RNA into a single strand of DNA using host nucleotides. It then converts this single-stranded DNA into double-stranded DNA, which is essential for the virus to integrate into the host genome.

What errors does reverse transcriptase typically make during the transcription process?

Reverse transcriptase is known for making random errors during the transcription process due to its poor proofreading activity. This lack of accuracy contributes to the high mutation rate of HIV, which helps it evade the host's immune system.

How does integrase facilitate the integration of HIV DNA into the host chromosome?

Integrase, an enzyme that comes with the virus, grabs the double-stranded DNA and carries it through a nuclear pore into the cell's nucleus. It then makes a nick in the host DNA, allowing HIV to insert itself into the host chromosome, which establishes a lifelong infection.

What is the function of the viral envelope protein?

The viral envelope protein serves as a key component in the infection process. It binds to the CD4 receptor and the chemokine coreceptor on T helper cells, leading to membrane fusion. After the viral genetic material is injected into the cell, the envelope protein remains on the cell surface.

How are viral proteins produced and assembled into new virions?

Viral proteins are produced through the translation of messenger RNAs that are transcribed from the integrated viral DNA. These proteins are then transported to the cell surface where they coalesce with envelope proteins. Along with RNA and enzymes, they form a complex that buds off the cell surface. Protease, another viral enzyme, digests the polyprotein chains, allowing the formation of mature virion structures.

What is the role of RNA polymerase in the production of new viral components?

RNA polymerase is responsible for transcribing the integrated viral DNA into messenger RNA. These mRNAs encode for different viral proteins, which are then translated by ribosomes at the rough endoplasmic reticulum, leading to the production of new viral components.

How does the process of budding lead to the release of new virions from the infected cell?

Budding is the process where the newly formed viral components, including RNA, proteins, and enzymes, coalesce at the cell surface and pinch off, forming a new virion. This budding occurs at the cell membrane, and the newly formed virions are released to potentially infect other cells.

Why is the maturation of the viral particle by protease essential for its infectivity?

The maturation process by protease is essential because it cleaves the polyprotein chains into their functional components, allowing the formation of the mature virion structures necessary for infectivity. Without this step, the virus would not be able to infect new cells effectively.

Outlines

00:00

🦠 HIV Infection Process

The paragraph explains the lifecycle of the HIV virus, starting with its structure as a retrovirus with an outer envelope and RNA. It details how the virus infects T helper cells using the CD4 receptor and chemokine coreceptor (CCR5). The virus then fuses with the host cell membrane, injecting its genetic material into the cell. The viral enzymes and RNA are released, and reverse transcriptase converts the viral RNA into DNA, which is then integrated into the host's DNA by integrase, leading to lifelong infection. The process continues with the production of viral proteins and the assembly of new virions, which are eventually released to infect other cells.

Keywords

💡Retrovirus

A retrovirus is a type of virus that carries its genetic information in the form of RNA and uses an enzyme called reverse transcriptase to convert its RNA into DNA. This is a defining feature of retroviruses, which allows them to integrate their genetic material into the host's genome. In the context of the video, HIV is described as a retrovirus with an outer envelope and two copies of RNA, which it uses to infect cells.

💡Envelope Protein

Envelope proteins are found on the surface of enveloped viruses and play a crucial role in the viral infection process by interacting with host cell receptors. In the video, the HIV envelope protein is mentioned as the component that binds to the CD4 receptor on T helper cells, initiating the infection process.

💡T Helper Cells

T helper cells, also known as CD4+ T cells, are a type of white blood cell that plays a central role in the immune system by helping to activate other immune cells. They are characterized by the presence of the CD4 molecule on their surface. In the video, T helper cells are identified as the primary target for HIV infection due to the presence of CD4 receptors.

💡Reverse Transcriptase

Reverse transcriptase is an enzyme produced by retroviruses that catalyzes the synthesis of DNA from an RNA template, which is a reverse of the usual flow of genetic information. This enzyme is vital for the life cycle of HIV, as it allows the virus to convert its RNA genome into DNA, which can then be integrated into the host cell's genome. The video script describes reverse transcriptase as an enzyme within the virus that turns RNA into DNA.

💡Chemokine Coreceptor

The chemokine coreceptor, also known as CCR5, is a protein on the surface of certain immune cells that, along with the CD4 receptor, HIV uses to enter the cell. It is a secondary receptor that HIV interacts with after binding to CD4. The video explains that the virus uses the chemokine coreceptor to further engage with the host cell and facilitate entry.

💡Fusion

Fusion in the context of viral infection refers to the process by which the viral envelope and the host cell membrane merge, allowing the viral contents to be released into the cell. The video describes how the HIV envelope protein's stalk punctures the host cell membrane, leading to the fusion of the viral and cellular membranes and the injection of viral genetic material.

💡Integrase

Integrase is an enzyme that retroviruses use to insert their DNA into the host cell's genome. This integration is a critical step in the viral life cycle, as it allows the virus to become a permanent part of the host cell's genetic material. The video script explains how integrase carries the viral DNA through the nuclear pore into the nucleus and inserts it into the host chromosome.

💡Messenger RNA (mRNA)

Messenger RNA is a molecule that conveys genetic information from DNA to the ribosomes, where it is translated into proteins. In the video, it is mentioned that once HIV's DNA is integrated, the host cell's RNA polymerase transcribes it into mRNA, which then encodes for various viral proteins necessary for the assembly of new virus particles.

💡Rough Endoplasmic Reticulum

The rough endoplasmic reticulum (ER) is a cellular organelle with ribosomes attached to its surface, where proteins are synthesized and processed. The video describes how the mRNA encoding for the HIV envelope protein associates with ribosomes at the rough ER, where the protein is produced and then transported to the cell surface.

💡Viral Budding

Viral budding is the process by which new virus particles are assembled and released from the host cell. It involves the formation of a viral envelope from the host cell membrane, which encases the viral components. The video script describes how the viral components, including RNA and enzymes, coalesce at the cell surface and bud off, forming immature virions that will later mature into infectious particles.

💡Protease

Protease is an enzyme that cleaves proteins, and in the context of HIV, it is crucial for the maturation of the virus. The video explains that protease breaks down the polyprotein chains into their functional components, allowing the virus to form the mature structures necessary for infectivity.

Highlights

HIV is a retrovirus with an outer envelope and two copies of RNA.

Reverse transcriptase enzyme turns viral RNA into DNA.

HIV infects T helper cells using CD4 molecule receptors.

Chemokine coreceptor CCR5 is also involved in HIV entry into cells.

Envelope protein of HIV causes membrane fusion with the host cell.

Viral genetic material is injected into the host cell, leaving the envelope protein behind.

Viral matrix and capsid proteins are digested upon cell entry, releasing viral enzymes and RNA.

Reverse transcriptase introduces errors due to its poor proofreading activity.

Integrase enzyme carries viral DNA into the nucleus and inserts it into the host chromosome.

Lifelong infection is established by HIV integration into the host DNA.

Viral proteins are encoded by messenger RNA and produced at the rough endoplasmic reticulum.

Envelope proteins are embedded in the cellular membrane and cluster on the cell surface.

Viral proteins and RNA coalesce to form a complex at the cell surface.

Protease enzyme digests polyprotein chains, allowing for the formation of mature virions.

Mature infectious virions can infect other cells, perpetuating the infection cycle.

HIV replication leads to the production of numerous viruses, maintaining the infection process.

Transcripts

SPEAKER: So this is HIV.

It's a typical retrovirus, meaning

that it has an outer envelope.

And in the center, it has two copies of RNA,

as well as an enzyme, here in blue.

That's reverse transcriptase, which will ultimately

turn that RNA into DNA.

The virus itself, with this outer envelope protein,

actually directly infects T helper cells.

The way that it does this is that as it comes up to the cell

surface, it uses receptors that are on T helper cells

and exclusive to T helper cells, which are CD4 molecule, which

really defines T helper cells.

It's a surface receptor that binds to the envelope protein.

That causes a conformational change

and allows a second receptor to grab hold of the envelope.

This is the chemokine coreceptor.

It's also called CCR5, and we'll talk about that more.

What happens now is that the stalk of the envelope protein

pierces through from the virus into the host cell

and starts to draw the cell membrane and the viral membrane

together.

And what ultimately happens is fusion of those two membranes.

And the viral genetic material is injected essentially

into the cell.

And the envelope protein is left at the cell surface.

The virus has a matrix and a capsid protein, shown here

in green and red, that essentially are digested

when it enters into the cell.

That releases viral enzymes in the viral RNA.

And here we have reverse transcriptase,

which takes the viral RNA, and using host nucleotides,

converts that viral RNA into a single strand of DNA.

While it does that, it makes some random errors,

which is characteristic of reverse transcriptase.

It has very poor proofreading activity.

That single-stranded DNA now is again reverse transcribed

into a double-stranded DNA.

At that point, another enzyme that

has come in with the virus in the beginning, called

integrase, essentially grabs hold

of that double-stranded DNA and carries it

through a nuclear pore into the nucleus of the cell.

Within the nucleus of the cell, it finds the host chromosome.

And basically, the integrase enzyme

makes a nick in the host DNA and allows for HIV

to insert itself into the host chromosome.

And that right there is what establishes lifelong infection.

Now, RNA polymerase comes along and makes messenger RNA.

Those messenger RNAs encode for different viral proteins.

They end up associating with ribosomes

at the surface of the rough endoplasmic reticulum.

And here's a piece of mRNA that's

making envelope protein, which is directly produced

into the endoplasmic reticulum.

And it's shuttled then through the endoplasmic reticulum

and taken to the cell surface, where at the cell surface,

it becomes embedded in the cellular membrane.

And at this point, coalescing with other envelope proteins

that have been produced, you have this cluster

of envelope proteins now on the surface of this infected cell.

At the same time, there are other messenger RNAs

that are being produced that allow for translation

of other viral proteins.

So here are additional viral proteins being made

which are going to be used to make up

the key components that the virus ultimately

is going to need.

These are transported again to the cell surface,

to the area where these envelope proteins are.

And a strand of RNA, as well as some of the enzymes

are part of that complex.

This then buds off at the cell surface at this point.

But it's still not a mature virion

because the polyprotein chain needs to still be digested

into its component parts.

That's done by an enzyme called protease.

Protease breaks up those polyprotein chains

and ultimately allows for them to coalesce and form

the mature structures that make up the final virion.

And now you have a mature infectious virion

that can go on now to infect other cells.

Once that happens now, the cell can produce tons of viruses,

and this is really what then keeps the whole process going.