5.4 Human Immunodeficiency Virus

An overview of the Human Immunodeficiency Virus (HIV), its structure, life cycle, the disease it causes (AIDS), and methods of treatment and prevention.

Introduction to HIV

• Human Immunodeficiency Virus (HIV): The causative agent of Acquired Immunodeficiency Syndrome (AIDS).
• It is a retrovirus, meaning it uses its RNA genome to synthesize a DNA intermediate in the host cell.
• First identified in 1984 and officially named HIV in 1986.

Structure of HIV

HIV is a spherical virus with a complex structure.

• Envelope: An outer lipoprotein envelope derived from the host cell's membrane during budding. Plasma Membrane→

  • Glycoprotein Spikes: Embedded proteins crucial for infection.
    • gp120: Outer glycoprotein that attaches to CD4 receptors on host cells.
    • gp41: Transmembrane glycoprotein critical for fusing the viral envelope with the host cell membrane.

• Matrix: A protein shell located between the envelope and the capsid.

• Capsid: A conical-shaped protein coat composed of capsomeres.

• Viral Core: Contains the essential components for replication.

  • Genetic Material: Two single strands of viral RNA.
  • Enzymes:
    • Reverse Transcriptase: Converts the viral RNA genome into a complementary DNA (cDNA) molecule.
    • Integrase: Incorporates the viral DNA into the host cell's DNA.
    • Protease: Cleaves large viral proteins into smaller, functional units for new virion assembly.

Life Cycle of HIV

HIV exhibits host cell specificity, primarily targeting cells with CD4 receptors, such as Helper T-cells, macrophages, and some brain cells.

1. Attachment (Adsorption): The viral glycoprotein gp120 binds to the CD4 receptor on the surface of a host cell (e.g., a Helper T-cell). Cell Signaling→

2. Penetration and Uncoating: The viral envelope fuses with the host cell membrane, a process mediated by gp41. The virion enters the cell via endocytosis, and its capsid breaks down (uncoating), releasing the viral RNA and enzymes into the cytoplasm. Endocytosis→

3. Reverse Transcription: The enzyme reverse transcriptase synthesizes a single strand of DNA (cDNA) complementary to the viral RNA.

4. RNA Degradation: The original viral RNA template is degraded by the enzyme ribonuclease (RNAase).

5. DNA Replication: The single-stranded cDNA is replicated to form a double-stranded viral DNA molecule.

6. Integration: The enzyme integrase incorporates the double-stranded viral DNA into the host cell's own DNA.

7. Provirus Stage: The integrated viral DNA is now called a provirus. It can remain dormant or become active.

8. Transcription: The host cell's RNA polymerase transcribes the proviral DNA, producing viral mRNA and new copies of the viral RNA genome.

9. Biosynthesis (Translation): Host cell ribosomes translate the viral mRNA into large viral proteins.

10. Cleavage: The enzyme protease cuts these large proteins into smaller, functional structural proteins and enzymes.

11. Maturation (Assembly): New viral RNA genomes and proteins assemble into new, immature virions.

12. Release: Mature virions are released from the host cell by budding, taking a portion of the host's cell membrane with them to form their own envelope. This process gradually depletes the host cell's membrane, rendering it non-functional and eventually killing it.

Pathogenesis: How HIV Causes AIDS

• Helper T-cells are crucial components of the immune system; they activate B-cells (to produce antibodies) and cytotoxic T-cells (to kill infected cells).
• By targeting and destroying Helper T-cells, HIV systematically weakens the immune system.
• The progressive decline in Helper T-cell count leads to a state of immunodeficiency, which is why the virus is named Human Immunodeficiency Virus.

Symptoms and Stages of AIDS

An HIV infection progresses through three main stages:

Opportunistic Diseases

• These are infections caused by pathogens that a healthy immune system would normally fight off.
• In AIDS patients, these pathogens take advantage of the weakened immune system.
• Examples include:
  • Skin Cancer (e.g., Kaposi's Sarcoma)
  • Fungal infections (e.g., Pneumocystis pneumonia, candidiasis)
  • Viral infections (e.g., Cytomegalovirus)
  • Gastrointestinal, respiratory, and nervous system diseases.

Treatment and Control

Treatment of AIDS

• Antiretroviral Therapy (ART): A combination of medicines used to fight HIV infection.
  • Function: ART is not a cure but can control the virus, allowing an HIV-positive person to live a longer, healthier life. It also reduces the risk of transmission.
  • Limitations: Can have toxic side effects, is costly, and requires strict daily adherence. A cure remains a major research goal.

Control Measures and Prevention

Prevention focuses on stopping the transfer of body fluids (blood, semen, etc.) from an infected person to an uninfected one.

Do:

• Use properly sterilized surgical instruments.
• Screen all blood for HIV before transfusion.
• Follow Islamic teachings and refrain from immoral sexual activities.

Do Not:

• Use or share used syringes and needles.
• Share personal items like toothbrushes, blades, or towels.
• An HIV-positive mother should not breastfeed her baby.

HIV is NOT Transmitted By:

• Shaking hands, hugging, coughing, or sneezing.
• Swimming in the same pool.
• Inanimate objects like toilets, doorknobs, or telephones.
• Mosquitoes or other insects.