HIV Structure, Lifecycle, and

Replication
Background: Basic Virology

Structure: Virion structure, genome,

and proteins

Lifecycle: Infection and Expression

skitchen@ucla.edu
 Viruses
Microscopic infectious agents that can infect the cells of a
biological organism.

Viruses can only replicate themselves by infecting a host cell

and are incapable to reproduce on their own.

A complete virus particle, known as a virion consists of nucleic

acid surrounded by a protective coat of protein called a capsid.
Human immunodeficiency virus (HIV) is a retrovirus that
causes acquired immunodeficiency syndrome (AIDS).

HIV primarily infects vital cells in the human immune

system such as helper T cells (CD4+ T cells),
macrophages and dendritic cells. HIV infection leads to
low levels of CD4+ T cells.

http://www.unaids.org/en/
The Natural History of HIV Infection
The “Enemy”
Basic Virology

Virus:

• Genomic “instructions” (RNA or DNA)

• Physical structure (envelope and capsid)

• Viral enzymes (reverse transcriptase,

accessory gene products)

• Parental host cell membrane

•~ 9,100 RNA bases in length

•Encodes 9 genes
HIV Structure

Virion

Genomic

Proteomic
HIV Proteins

Structural Proteins
Gag: Matrix, Capsid, NC
Pol: Protease, Reverse Transcriptase, Integrase
Env: gp120, gp41

Regulatory Proteins
Tat
Rev
Nef

Accessory proteins
Vif
Vpr
Vpu
HIV Lifecycle:
 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 antagonist, maraviroc
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

B. Fusion Inhibitors:
Fusion & uncoating
T20
 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

In
fe
ct
io
Fusion & Entry
n

Binding

Reverse
transcription Nuclear
localization
CD4 & entry
Integration

CXCR4
 Viral RNA
gp120
p24
Assembly

RT & other
virion prteins Post-translational
processing

Budding

Translation

Ex
pr Viral Gene
es Transcription

s ion
 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
 Discussion Points/Exercises
1) Can you draw a representation of what HIV
looks like?

2) Explain, in general lay terms in 1 sentence,

how an HIV entry inhibitor, reverse
transcriptase inhibitor, integrase inhibitor, and
protease inhibitor work based on your
knowledge of the HIV lifecycle.

3) Discuss where you think other targets for

antiretroviral therapy may be based on its
lifecycle.