HIV / AIDS

Introduction
The Human Immunodeficiency Virus or HIV virus as it
is commonly known is a unique type of virus (a
retrovirus, retro (backwards)). The human
immunodeficiency virus causes the acquired
immunodeficiency syndrome, a condition in humans
in which progressive failure of the immune system
allows life-threatening opportunistic infections and
cancers to thrive.
The HIV Virus:

• Invades the helper T cells (CD4 cells) in the body of the

host (defense mechanism of a person).
• Is threatening a global epidemic.
• Is preventable & manageable but is NOT curable.
Former names of the virus include:

• Human T cell lymphotrophic virus (HTLV-III)

• Lymphadenopathy associated virus (LAV)
• AIDS associated retrovirus (ARV)
 AIDS (acquired immune deficiency syndrome) is the final
stage of HIV disease, which causes severe damage to the
immune system.
• HIV is the virus that causes AIDS.
• Disease limits the body’s ability to fight infection due to
markedly reduced helper T cells.
• Patients have a very weak immune system (defense
mechanism).
• Patients predisposed to multiple opportunistic infections
leading to death.
• AIDS Predisposes our body to other
opportunistic infections.

• Opportunistic infections and malignancies

that rarely occur in the absence of severe
immunodeficiency (e.g. Pneumocystis
pneumonia, central nervous system
lymphoma).
 enveloped virus subfamily of
retroviruses. Retroviruses
transcribe RNA to DNA.

Two viral strands of RNA found in core

surrounded by protein outer coat.
The “Enemy”
HIV Lifecycle:
• Blood products
• Semen
• Vaginal fluids
 Sharing Needles
Without sterilization Increases the chances of
contracting HIV
 Unsterilized blades
• Before Birth
• During Birth
Three Phases of HIV
Phase 1- Asymptomatic Stage
 Short, flu-like illness, swollen glands, fatigue, diarrhea,
weight loss, or fevers - occurs one to six weeks after
infection
 no symptoms at all
 Infected person can infect other people
 Lasts for an average of ten years
 HIV antibodies are detectable in the blood
 Phase 2 - Symptomatic

 The symptoms worsen

 Mental changes, forgetfulness & abnormal thinking
patterns
 Phase 3 - HIV  AIDS

 Immune system
weakens
 Emergence of
opportunistic
infections and cancers
 The illnesses become
more severe leading
to an AIDS diagnosis
The immune system
weakens too
Opportunistic Infections associated
with AIDS

 Bacterial
 Tuberculosis (TB)
 Pneumocystis pneumonia

 Viral
 Kaposi Sarcoma-purple-red
blotches on the skin
 Influenza (flu)
• Nucleoside Reverse Transcriptase inhibitors
• Non-Nucleoside Transcriptase inhibitors
Protease inhibitors
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion
proteins

Binding

CD4

CXCR4 or CCR5
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion
proteins

Binding A. Entry Inhibitors:

CCR5

CD4

CXCR4
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Fusion & uncoating

 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion
proteins

Fusion & uncoating

B. Fusion Inhibitors:
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Reverse
transcription
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion C. Reverse Transcriptase (RT) Inhibitors:
proteins
1. Nucleoside RT inhibitors (NRTIs)
2. Non-Nucleoside RT Inhibitors NNRTIs)

Reverse
transcription
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Nuclear
localization
& entry
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Integration
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion
proteins
D. Integrase Inhibitors:
raltegravir

Integration
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Integrated
provirus
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Integrated
provirus
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Viral Gene
Transcription
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

Translation
 HIV Lifecycle:
Viral RNA
gp120 Post-translational
p24 processing

RT & other
virion prteins
 HIV Lifecycle:
Assembly

Viral RNA
gp120
p24

RT & other
virion prteins
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins Budding
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion Budding
proteins

Inhibition of Virion Maturation

E. Protease Inhibitors:
e.g. Lopinavir, Indinavir
 HIV Lifecycle:
Viral RNA
gp120
p24

RT & other
virion prteins

This process averages about 1.2 days

 Viral RNA
gp120
p24

RT & other
virion
proteins

Fusion & Entry

Binding

Reverse
transcription Nuclear
localization
CD4 & entry
Integration

CXCR4
 Viral RNA
gp120
p24
Assembly

RT & other
virion prteins Post-translational
processing

Budding

Translation

Viral Gene
Transcription
 Some Take-home points:
HIV Structure:

– HIV is comprised of viral proteins, host cell membrane

– env is the only exposed viral protein (evades immune

response)

– gag (p24) represents the primary structural component of

virion
 Take-home points:

HIV Genome:

– RNA genome -- requires HIV reverse transcription to

DNA

– In a productive infection, genome permanently

integrates into host genome

– HIV Genome encodes 9 viral genes: 3 structural, 3

regulatory, 3 accessory