HIV & AIDS: Structure, Replication, and Treatment

HIV & AIDS: Structure, Replication, and Treatment

Introduction to HIV and AIDS

Human Immunodeficiency Virus (HIV) is a retrovirus that targets the immune system, leading to Acquired Immunodeficiency Syndrome (AIDS) if untreated. Understanding the structure, genome, replication, and treatment of HIV is crucial in microbiology and medicine.

Key Definitions

• HIV (Human Immunodeficiency Virus): A virus that attacks and weakens the human immune system, specifically targeting CD4+ T cells.

• Retrovirus: A type of RNA virus that uses reverse transcriptase to convert its RNA genome into DNA, which integrates into the host cell genome.

• AIDS (Acquired Immunodeficiency Syndrome): The advanced stage of HIV infection, characterized by a severely weakened immune system and increased susceptibility to opportunistic infections and certain cancers.

Structure of HIV

• Envelope: The outer lipid membrane derived from the host cell, containing viral glycoproteins (gp120 and gp41).

• Capsid: A protein shell (p24) that encases the viral RNA genome and essential enzymes.

• Genome: Two single-stranded RNA molecules.

• Enzymes: Reverse transcriptase, integrase, and protease are packaged within the virion.

Example: Drawing an annotated HIV virion should include the envelope, capsid, RNA genome, and enzymes.

HIV Genome Organization

• The HIV genome contains several genes, including gag, pol, and env, which encode structural proteins, enzymes, and envelope proteins, respectively.

• Accessory genes (e.g., tat, rev, nef, vif, vpr, vpu) regulate viral replication and modulate host immune responses.

Functions of Viral Proteins

• Structural proteins: Form the capsid and envelope (e.g., p24, gp120, gp41).

• Enzymes: Reverse transcriptase (RNA to DNA), integrase (integration into host genome), protease (protein processing).

• Accessory proteins: Enhance replication, evade immune detection, and regulate gene expression.

HIV Replication Cycle

• Attachment: HIV gp120 binds to CD4 receptors and co-receptors (CCR5 or CXCR4) on target cells.

• Fusion and Entry: Viral envelope fuses with the host cell membrane, releasing the capsid into the cytoplasm.

• Reverse Transcription: Viral RNA is reverse transcribed into DNA.

• Integration: Viral DNA integrates into the host genome via integrase.

• Transcription and Translation: Host machinery produces viral proteins and RNA genomes.

• Assembly: New virions are assembled at the cell membrane.

• Budding and Maturation: Virions bud from the cell and mature via protease activity.

HIV Tropism and Pathogenesis

• Cell Tropism: HIV preferentially infects CD4+ T cells, macrophages, and dendritic cells.

• Replication in Target Cells: The virus exploits host cell machinery for replication, leading to cell death and immune suppression.

• Pathogenesis: Progressive loss of CD4+ T cells impairs immune function, resulting in AIDS.

Stages of HIV Infection

• Acute infection: Rapid viral replication and initial immune response.

• Clinical latency: Low-level replication; patient may be asymptomatic.

• Symptomatic infection: Immune system declines, opportunistic infections appear.

• AIDS: Severe immunodeficiency and life-threatening infections or cancers.

Immune Response to HIV

• Both innate and adaptive immunity are activated, but HIV evades immune detection through rapid mutation and destruction of immune cells.

Treatment of HIV Infection

• Antiretroviral drugs: Inhibit various stages of the HIV life cycle (e.g., reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, entry inhibitors).

• HAART (Highly Active Antiretroviral Therapy): Combination of three or more antiretroviral drugs to suppress viral replication and prevent resistance.

• Combination therapy: Reduces the risk of drug resistance and improves treatment efficacy.

Drug Class	Target	Example
Reverse Transcriptase Inhibitors	Reverse transcription	AZT (zidovudine)
Protease Inhibitors	Viral maturation	Ritonavir
Integrase Inhibitors	Integration of viral DNA	Raltegravir
Entry Inhibitors	Viral entry into cells	Maraviroc

Example: HAART typically includes two nucleoside reverse transcriptase inhibitors and one protease or integrase inhibitor.

Additional info: Combination therapy is essential to prevent the emergence of drug-resistant HIV strains and to maintain long-term viral suppression.