Biology (9610) | HIV as an example of a human disease caused by a virus

🔬 Unit 2: Biological Systems and Disease – HIV and Viral Pathogenesis

Welcome to one of the most crucial topics in disease biology: understanding the Human Immunodeficiency Virus (HIV). These notes will break down the structure of this unique virus and explain, step-by-step, how it replicates inside human cells—a process that ultimately cripples the immune system.

Don't worry if viruses seem complicated; they are just packages of genetic material with highly specific instructions. We will tackle the structure first, and then follow its journey inside the cell.

3.2.4.1 The Structure of HIV

HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). It is an example of a retrovirus—a special class of virus that uses RNA as its genetic material and converts it into DNA inside the host cell.

Imagine the HIV virus as a tiny, highly specialized delivery package. Here are the essential components you must know:

Key Components of the HIV Structure

• Genetic Material (The Blueprint): HIV contains its genetic information in the form of two identical single strands of RNA. Since RNA is usually unstable, having two copies provides a backup.
• Protein Capsid (The Inner Shell): A cone-shaped layer of protein that encloses the genetic material and the viral enzymes. This provides protection.
• Envelope (The Outer Coating): This outer layer is actually taken from the plasma membrane of the previous host cell when the virus buds off. It makes the virus sensitive to things like soap and heat.
• Glycoproteins (The Keys): Studded within the envelope are specific protein molecules (antigens), known as glycoproteins. These act like "keys" that allow the virus to bind to and enter target host cells.

The Essential Viral Enzymes (The Tools)

Inside the capsid, alongside the RNA, are three crucial enzymes that HIV needs to hijack the host cell's machinery. Without these, replication cannot occur.

1. Reverse Transcriptase (RT): This is the most famous HIV enzyme. It uses the viral RNA template to synthesize a complementary strand of double-strand DNA. This step is unique to retroviruses.
2. Integrase: This enzyme is responsible for 'stitching' the newly created viral DNA into the host cell's own DNA chromosome.
3. Protease: This enzyme cuts long chains of viral proteins (polypeptides) into their final, functional forms during the assembly stage, preparing the new virus particles for release.

Quick Memory Aid: You can remember the three enzymes as R.I.P. (Reverse Transcriptase, Integrase, Protease).

3.2.4.2 The Replication Cycle of HIV

The main target cells of HIV are CD4 helper T-cells. These cells are vital because they initiate and coordinate the entire adaptive immune response to infections. By destroying these T-cells, HIV effectively wipes out the body's defensive command center, leading to AIDS.

Step-by-Step: Hijacking a Helper T-Cell

The replication process is a precise sequence of events:

1. Binding and Entry (Attachment):

• The glycoproteins on the HIV envelope bind specifically to the CD4 receptors found on the surface of the helper T-cells.
• This specific binding triggers the fusion of the viral envelope with the host cell's plasma membrane, allowing the virus contents to be released into the cytoplasm.

2. Release of Contents:

• The protein capsid breaks down, releasing the viral components: the two strands of RNA and the essential viral enzymes (Reverse Transcriptase, Integrase, Protease).

3. Reverse Transcription:

• The enzyme Reverse Transcriptase takes the viral RNA template and synthesizes a complementary strand of DNA.
• It then uses this DNA strand to produce a double-strand DNA copy of the viral genome.
• Analogy: RT acts as a specialized translator, converting the viral language (RNA) into the host cell's language (DNA).

4. Integration:

• The newly formed viral DNA enters the host cell nucleus.
• The enzyme Integrase cuts the host cell's chromosome and inserts the viral DNA, making it a permanent part of the host cell's genetic material.
• At this point, the host cell is permanently infected. The integrated viral DNA is now called a provirus.

5. Viral Transcription and Synthesis:

• When the infected T-cell is activated, its own machinery (RNA polymerase) begins transcribing the DNA, including the integrated viral DNA.
• This process produces new strands of viral RNA (which will serve as the genetic material for new viruses) and also new viral proteins (which form the capsid and enzymes).

6. Assembly and Budding (Release):

• The new viral RNA and proteins migrate to the cell surface. Long protein chains are cut into functional components by the Protease enzyme.
• The new virus particle is packaged and then 'buds' off the host cell, taking a piece of the host's plasma membrane with it to form its outer envelope.
• This process often destroys the host T-cell, leading to the progressive collapse of the immune system over time.

Key Takeaway: The defining feature of HIV replication is the conversion of RNA into DNA, which is then integrated into the host genome. This is what makes it so difficult to cure.

Applying Knowledge: The Role of HIV Drugs

Your knowledge of the HIV structure and replication cycle allows you to understand how modern treatments work. Scientists target the specific steps unique to the virus, ensuring minimal harm to the host cell.

How Anti-Retroviral Drugs Work

Current treatments often involve a cocktail of drugs (called HAART – Highly Active Anti-Retroviral Therapy), each targeting a different viral enzyme or step:

1. Reverse Transcriptase Inhibitors (RTIs):

• These drugs block the action of the Reverse Transcriptase enzyme (Step 3).
• If the viral RNA cannot be converted into DNA, the virus cannot integrate its genome and replicate, effectively halting the infection process in new cells.

2. Integrase Inhibitors:

• These drugs block the action of the Integrase enzyme (Step 4).
• They prevent the viral DNA from being successfully "stitched" into the host cell's chromosome.

3. Protease Inhibitors (PIs):

• These drugs block the action of the Protease enzyme (Step 6).
• If this enzyme is blocked, the newly synthesized viral proteins cannot be cut into their correct functional shapes, meaning new virus particles are produced but are non-infectious (defective).

By using a combination of these inhibitors, drug therapy significantly slows the replication rate, reducing the viral load and allowing the CD4 helper T-cell count to recover, thus preventing the progression to AIDS.

Common Mistake to Avoid: HIV drugs do not *kill* the virus; they inhibit the enzymes required for replication. They stop the infection from spreading to new cells and reduce the viral population in the body.