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What is a virus?
 “Genes in a suitcase”
 Composition of a virus particle or virion:
Genes
Suitcase
Envelope
RNA or DNA
Protein shell
Viral proteins
Minimum requirement
 Mode of replication:
• Use host machineries for replication
• Assemble in host cells
Viruses vs. Bacteria
Bacteria Viruses
Very small or “filterable” (20-250 nm)
No
Most
Contain both DNA and RNA
Growth on non-living medium
Metabolism
Yes
No
Most
No
Yes
No
Human Immunodeficiency virus (HIV)
 Retrovirus
 Virion =
•RNA genome
•Capsid
•Envelope (host)
•Viral proteins
Capsid
RNA
Envelope
 causative agent for Acquired Immunodeficiency
Syndrome (AIDS)
HIV (Virus) ≠ AIDS (Disease)
 infects macrophages and CD4 T-lymphocytes
 Virus life cycle: multi-step events, use host machinery
A global view of HIV infection in 2008: 33.4
million people living with HIV
Note: This map represents 2007. Source: WHO/UNAIDS, 2008.
Please explain why the following
statements are incorrect.
1. HIV and AIDS is the same thing.
2. There is a cure for HIV.
3. In the absence of antiretroviral therapy, all
individuals who are exposed to HIV will
eventually progress to AIDS.
4. Mosquito can transmit HIV.
What is the scientific process?
Individuals respond differently to HIV infection
Antiretroviral therapy
Exposed to HIV
~1%
90-95%
AIDS
>10,000 copies
RNA/mL
“Progressor”
5-10%
No AIDS
(<200 copies RNA/mL)
“Intermediate
Controller”
No AIDS
Undetectable viral RNA
“Elite Controller”
Do not require
antiretroviral therapy
Based on the observation, propose a hypothesis that explains the differences
between the Progressors and Controllers. (Hint: think about what factor(s) maybe
responsible for the development of AIDS in patients. Use information on the life
cycle.)
What method(s) will you use to test your hypothesis?
What are you expected outcomes?
Information obtained from Kaur and Mehra (2009) Tissue Antigens 73, 289–301
11. Maturation
Protease
1. Entry
gp120, gp41
CD4, CCR5, CXCR4
10. Release
Gag
CD4-positive
T-lymphocytes
2. Reverse transcription
Reverse transcriptase
9. Assembly
Gag
8. Translation
ribosomes
3. Uncoating
7. RNA Export
rev
importins
4. Nuclear import
5. Integration
Integrase, p32
6. Transcription
Tat
Host transcription
machineries
Host proteins
Viral proteins
Figure was modified from Arhel N, Kirchhoff F. Biochim Biophys Acta. 2010
Host genetic vs. progression to AIDS

Genetic association study: progressors vs. controllers
 Mutations on host proteins delay progression to AIDS
(HIV controllers)
 Entry receptors for HIV
• CCR5∆32
M. Dean et al., Science 273, 1856 (1996).
• C927T in CCR5
M. P. Martin et al., Science 282, 1907 (1998).
• Val64Ile in CCR2
M. W. Smith et al., Science 277, 959 (1997).
 Immune response against HIV
• Major histocompatibility complex (MHC) class I - single
nucleotide polymorphisms (SNPs) The International HIV
controllers study, Science 330, 1551 (2010)
SNPs in many host factors involved in HIV
infection could associate with AIDS progression
Host factors that are important for the following host processes are also involved
in HIV infection
Surface molecules
Signaling
Cytoskeleton
Nuclear import
Endocytosis
Chromatin
Nuclear export
RNA splicing
Intracellular
receptors
Proteasomal
degradation
Lysosomal
degradation
Transcription &
DNA binding
Translation
RNA binding
Protein assembly
Metabolism
Apoptosis
Protein
modification
Cell cycle &
proliferation
Cytokines
Information obtained from Arhel N, Kirchhoff F. Biochim Biophys Acta. 2010
How can we use host genetic information to help
control HIV pandemic???
Challenges in controlling HIV pandemic
What methods are used to prevent HIV infection or
spread?
Will SNPs information help prevent HIV infection in
countries with high infection rate?
Other resources
TWiv: This week in Virology
Weekly Podcast about viruses
http://www.twiv.tv/
CDC: Centers for Disease
Control and Prevention
http://cdc.gov/
Institute for Molecular Virology
UW Virology Resources: Labs,
links, images
http://www.virology.wisc.edu/
ProMED
The global electronic reporting
system for outbreaks of emerging
infectious diseases & toxins
http://www.promedmail.org
UNAIDS: Joint United Nations
Programme on HIV/AIDS
http://www.unaids.org/en/def
ault.asp