HIV Recorded Lecture

HIV Life Cycle Overview

HIV (Human Immunodeficiency Virus) is a retrovirus from the lentivirus family that replicates through the reverse transcriptase enzyme, incorporating its genetic material into the DNA of host cells. Understanding the seven steps of the HIV life cycle is crucial for comprehending antiretroviral medications and their mechanisms of action.

Importance of the Life Cycle

• Antiviral/Atriretroviral Therapy Alignment: The steps in the HIV life cycle align with the antiretroviral medications used to treat HIV, making it essential for understanding treatment options.

• Study Strategy: Familiarity with the life cycle can help in grasping medication classes and their purposes in HIV treatment.

HIV Characteristics

• HIV has significantly evolved over the past three decades, transitioning from a terminal illness to a manageable chronic disease for many patients. However, the experience can vary; not all patients will have the same outcomes.

• HIV attacks the immune system, specifically targeting CD4 T cells, making individuals vulnerable to opportunistic infections.

Overview of HIV Structure

• Retrovirus Definition: Retroviruses, like HIV, carry RNA and must convert this RNA into DNA (double-stranded) to integrate into the host's genetic material using reverse transcriptase.

• Types of HIV: There are two main types—HIV-1 (predominantly worldwide) and HIV-2 (more common in certain parts of Africa).

Steps of the HIV Life Cycle

Step 1: Binding

• Attachment to CD4 Cells: HIV binds to the CD4 receptor on the surface of T helper cells and requires co-receptors (CCR5) for effective attachment.

• Antagonists: Medications like CCR5 antagonists can block this initial binding to prevent infection.

Step 2: Fusion

• Membrane Fusion: The HIV envelope fuses with the CD4 cell membrane, allowing the viral genetic material entry into the cell's cytoplasm.

• Fusion Inhibitors: These drugs can halt the fusion process, preventing HIV entry into the host cell.

Step 3: Reverse Transcription

• RNA to DNA Conversion: Inside the CD4 cell, HIV uses reverse transcriptase to convert its RNA into double-stranded DNA.

• Reverse Transcriptase Inhibitors: Medications in this class stop the conversion process, preventing HIV from replicating.

Step 4: Integration

• Integration into Host DNA: The enzyme integrase helps HIV DNA integrate into the host cell's DNA.

• Integrase Inhibitors: These drugs can inhibit this integration step, halting the viral life cycle.

Step 5: Replication

• Viral Protein Production: Once integrated, HIV uses the host cell's machinery to produce long chains of viral proteins necessary for creating new viruses.

Step 6: Assembly

• HIV Particle Formation: Newly synthesized HIV proteins and RNA gather at the cell surface, forming immature HIV particles.

Step 7: Budding

• Release of New HIV: The newly formed immature HIV particles bud off from the CD4 cell and undergo proteolytic processing by the protease enzyme, resulting in mature HIV capable of infecting new cells.

• Protease Inhibitors: These medications interfere with the cleavage of viral proteins necessary for producing infectious HIV.

Key Enzymes to Remember

• Reverse Transcriptase: Converts HIV RNA to DNA (Inhibitors act here).

• Integrase: Integrates viral DNA into host DNA (Inhibitors act here).

• Protease: Cleaves long protein chains into functional proteins (Inhibitors act here).

Conclusion

Understanding the HIV life cycle is critical not only for grasping the mechanisms of antiviral and antiretroviral therapy but also for recognizing the importance of each medication class in targeting specific stages of replication. Leverage the seven steps as a framework for studying and connecting with the relevant pharmacological interventions.