HIV Life Cycle | HHMI BioInteractive Video
Summary
TLDRThe 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
🦠 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.
Mindmap
Keywords
💡Retrovirus
💡Envelope Protein
💡T Helper Cells
💡Reverse Transcriptase
💡Chemokine Coreceptor
💡Fusion
💡Integrase
💡Messenger RNA (mRNA)
💡Rough Endoplasmic Reticulum
💡Viral Budding
💡Protease
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.
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