3. Viral Infection & Immunomodulation [HIV & AIDS]

Learning Objectives

  • Define acquired immunodeficiency

  • Discuss the effect of HIV on the immune system

  • Explain possible diagnostic tests and relate to HIV Structure

  • Discuss treatment of HIV infection, including mode of action and relate to the life cycle of HIV

What is acquired deficiency?

  • Full or partial impairment of the immune system

What is AIDS?

applies to the most advanced stages of an HIV infection

What is HIV?

The virus that targets cells of the immune

  • Retrovirus

    • envelopes RNA viruses

    • uses reverse transcriptase in the conversion of viral RNA to DNA which is then incorporated into the host genome

  • 2 types

    • HIV-1 more aggressive global epidemic

    • HIV-2 (West Afrca)

What is HIV Structure

Capsid

Protein shell

Made up of capsid proteins, p .

Contains 2 strands of RNA (viral genome)

Envelope

Outer surface (phospholipid bilayer derived from the membrane of the host cell.)

Enzymes

Proteins that carry out steps in the HIV life cycle

Glycoproteins

Protein “spikes” embedded in envelope. G are anchored to the

virus via interactions with the transmembrane protein g

Matrix Shell

A matrix shell comprising approximately 2000 copies of the matrix protein (MA, p )

lines the inner surface of the viral membrane

Protease

cuts up precursor proteins into proteins

Reverse transcriptase

Converts RNA into DNA

Integrase

inserts viral DNA into the host chromosomal DNA

P6

Multiple roles.

Important for the formation of infectious viruses

What are 7 stages of HIV lifecycle

All Frogs Ride In Rainy Autumn Breezes.

  1. Attachment

  • HIV binds to CD4+ receptors on helper T cell lymphocyte

  • Co-receptor CXCR4 or CCR5 facilitates fusion

  1. Fusion

  • Membrane fusion occurs as the hydrophilic and hydrophobic regions interact with each other

  • The core of the virion is released into the host cell cytoplasm and the two RNA strands are released

  1. Reverse Transcription

  • Viral cDNA synthesis

  • Reverse transcriptase converts viral RNA to cDNA

  1. Integration

  • cDNA is transported to the nucleus by integrase

  • Integration is probably a random event but relies upon transcriptionally active sites

  1. Replication

  • Host cell produces new viral RNA

  • New viral RNA used as genomic DNA

  • New viral proteins synthesised

  1. Assembly

  • New viral RNA and proteins move to the cell surface

  1. Budding

  • Host cell membrane buds off releasing mature virion from cell

  • The new virus leaves the host cell to infect other cells

To help you memorize the sequence "A F R I R A B," we can create a mnemonic sentence where each word starts with the corresponding letter. Here’s a suggestion:

This sentence can help you recall the letters in the sequence:

  • All

  • Frogs

  • Ride

  • In

  • Rainy

  • Autumn

  • Breezes

What are the HIV effects on immune system

What are the HIV diagnostic factors

  • Sore throat

  • Fever

  • Enlarged lymph glands

  • Rash

  • Muscle aches

  • Sweating during the night

  • Twitching

  • Fatigue

  • Mouth ulcers

What tests are done to determine HIV diagnosis?

Enzyme-linked Immunosorbent assay (ELISA)

  • 4th generation = HIV Antigen/Antibody Combination Test

    • detects HIV in the blood by identifying either the:

    • HIV-1 p24 (coffin shaped capsid in virus) antigen or HIV antibodies.

  1. Western Blot

  2. Reverse Transcription-Polymerase Chain Reaction (RT-PCR)

  1. CD4+ Count - Flow cytometry

  1. HIV Nucelic acid test - NATS

What are the current treatments for HIV now

Antiretroviral therapy (ART)

  • a combination of HIV medicines (a treatment regime) to be taken every day

  • ART recommended for all HIV infected patients

  • main goal is to reduce a person’s viral load to an undetectable level.

  • Shown to reduce disease progression

  • Decrease comorbid disease

  • Prevent transmission

how does it work?

blocking any part of the lifecycle will prevent stages of lifecycle to occur