HIV/AIDS Overview and Structure

HIV/AIDS Overview

• HIV (Human Immunodeficiency Virus) is a virus that attacks the body's immune system, specifically CD4+ T cells.
• AIDS (Acquired Immunodeficiency Syndrome) is the final stage of HIV infection, characterized by severe immune system damage, vulnerability to infections, and certain cancers.
• Without treatment, HIV can progress to AIDS. However, with proper treatment (ART), individuals can live long, healthy lives.
• Globally, approximately 38 million people are affected by HIV, with many lacking access to treatment.

HIV Structure

• HIV is a virus that requires a host cell to reproduce.
• Key components of the HIV virus: -Gag: forms group specific protein antigens (p24 and p18) -Env: forms envelope proteins (gp120 and gp41) crucial for cell entry and interaction. -Enzymes: -Reverse transcriptase: converts viral RNA to DNA. -Protease: cuts proteins to allow for the proper functioning of viral proteins. -Integrase: inserts viral DNA into the host cell's DNA to allow for replication.

HIV Pathogenesis

• HIV spreads through bodily fluids (unprotected sex, sharing needles, mother-to-child transmission).
• HIV targets CD4+ T cells, crucial for immune function.
• Viral replication: HIV hijacks the host cell's machinery to create new viruses.
• Immune system breakdown: HIV gradually destroys CD4+ T cells, weakening the immune system, leading to opportunistic infections.
• Progression to AIDS: if untreated, the immune system becomes severely compromised, resulting in an increased vulnerability to infections and diseases.

HIV Entry into Cells

• HIV attaches to the CD4 receptor on the surface of CD4+ T cells.
• HIV binds to another receptor on the T cell (CCR5).
• HIV fuses with the T cell membrane, allowing viral RNA and enzymes to enter the cell for replication.

HIV Replication

• HIV replicates inside the host cell, converting RNA to DNA by reverse transcriptase.
• Viral DNA integrates into the host cell's DNA with help from the enzyme integrase.
• Host cell machinery produces new HIV RNA and proteins.
• New virus particles assemble and bud from the host cell, often killing the cell in the process, to infect other cells.

HIV Replication & Reverse Transcription

• HIV's RNA genetic material is copied into DNA via reverse transcriptase.
• Viral DNA integrates into the host cell's DNA, using the enzyme Integrase.
• Host cell machinery starts producing new HIV RNA and proteins.
• New virus particles assemble and exit the host cell.

Immune Response to HIV

• The body's innate immune system tries to detect and destroy HIV via dendritic cells and macrophages.
• The body activates CD8+ T cells to kill infected cells.
• However, HIV targets CD4+ T cells, impacting the overall immune response, particularly over time, leading to immune exhaustion.

Clinical Stages of HIV Infection

• Acute HIV infection: initial stage, flu-like symptoms, rapid viral replication.
• Chronic HIV (clinical latency): HIV is active, but at low levels; few symptoms for many years.
• AIDS: severe immune damage; opportunistic infections, cancers, and dementia are possible.

Symptoms of AIDS

• Opportunistic infections (e.g., Pneumocystis pneumonia, tuberculosis)
• Malignancies (e.g., certain cancers)
• Neurological effects (e.g., memory problems, confusion, HIV-associated dementia)

Diagnosis of HIV/AIDS

• ELISA testing: screens for HIV antibodies.
• Western blot: confirms HIV antibodies.
• Viral load test: measures HIV RNA levels to track disease and response to treatment.
• CD4 count: monitors the strength of the immune system by measuring the number of CD4 cells.

Antiretroviral Therapy (ART)

• ART involves a combination of medications that target different stages of the HIV life cycle, to block replication.
• ART helps lower the viral load and restore the immune system.
• Adherence to ART is vital; missing doses can lead to drug resistance.

Molecular Targets of ART

• Reverse transcriptase
• Integrase
• Protease
• Fusion inhibitors: block HIV entry, including Fuzeon, and enfuvirtide.
• CCR5 Antagonists: block CCR5 receptors on certain immune cells to restrict HIV entry.

HIV Transmission

• HIV transmission occurs through bodily fluids (blood, semen, vaginal fluids, breast milk). 

Prevention of HIV

• Safe sex practices (condoms, dental dams).
• Pre-exposure prophylaxis (PrEP): daily medication for at-risk individuals to reduce the risk of infection.
• Post-exposure prophylaxis (PEP): medication taken after potential exposure.

SARS-CoV-2 Infection

• SARS-CoV-2 is a virus that causes COVID-19.
• The virus enters cells via the ACE2 receptor.
• Proteolytic cleavage enables the virus to make its way into the cytosol.
• Viral genome will produce RNA and other proteins.
• Virus buds from the host cell with host membrane as its outer layer.
• Various approaches to combat infection with SARS-CoV-2 exist including monoclonal antibodies and antiviral drugs.

Explore the fundamentals of HIV and AIDS, including how the virus attacks the immune system and the importance of treatment. Additionally, learn about the structure of the HIV virus and its key components crucial for its replication and interaction with host cells.