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HIV VIRUS

Human Immunodeficiency Virus


HIV
K.F Motha 056029
T.V Rajaguru 056123
Content
• Introduction of HIV
• Classification of HIV
• Virus structure
• HIV replication
• Transmission
• HIV testing
• Antiretroviral therapy and treatments
• Vaccination strategies
HIV

• The virus that lead to Acquired


Immunodeficiency Syndrome (AIDS)

• AIDS is a condition that the immune


system begins to fail, leading to life-
threatening by opportunistic infections
Classification of HIV
• Group:Group VI (ssRNA-RT)
• Family: Retroviridae
• Genus: Lentivirus

• Two species of HIV infect humans


HIV-1 -more virulent, highly transmittable
HIV-2 -more virulent, less transmittable
Virus Structure
• Roughly spherical, diameter of about 120 nm
• Around 60 times smaller than a RBC.
• Composed of

– Envelope- 72 spikes, formed from the proteins gp120 and


gp41, matrix which is made from the protein p17

– Protein coat/ capsid- bullet-/conical shaped & composed of


2,000 copies of the viral protein p24

– Nucleic Acids- 02 copies of positive ss-RNA


The proteins gp120 and gp41 together make up the spikes
that project from HIV particles, while p17 forms the matrix
and p24 forms the core.
• HIV RNA codes for nine genes
1. gag
2. Pol Structural proteins
3. env
4. tat
5. rev
6. nef Infection, Replication &Pathogenicity
7. vif
8. Vpr
9. vpu
• Either ends of each of RNA strand have a long
terminal repeat, which helps to control HIV replication
The ss-RNA is tightly bound to

– Nucleocapsid proteins
– p17
– Enzymes
• HIV reverse transcriptase
• HIV proteases
• HIV ribonuclease &
• HIV integrase
HIV Replication cycle
• HIV can infect a variety of immune cells such as
– CD4+ T cells,
– Macrophages
– Microglia cells
– Dendritic cells

• When Infected 02 possible pathways:


1.Virus becomes latent
2.Virus becomes active (fast replication cycle,
1000 – 10,000 million virions /day.)
Steps of replication:

1. Entry

2. Reverse Transcription and Integration

3. Transcription and Translation

4. Assembly

5. Budding and Maturation


1. Entry

• Virus particle bumps into a cell that carries on its


surface a special protein called CD4

• The spikes on the surface of the virus particle


stick to the CD4

• Allow the viral envelope to fuse with the cell


membrane

• The contents then released into the human cell,


leaving the envelope behind
2. Reverse Transcription and
Integration
• Inside the cell, the HIV enzyme reverse
transciptase converts the viral RNA into DNA

• This DNA is transported to the cell's nucleus

• It is spliced into the human DNA by the HIV


enzyme integrase, integrated HIV DNA is known
as provirus
3. Transcription and Translation

• HIV provirus may lie dormant within a cell for a


long time

• First it converts them into m-RNA (using human


enzymes)

• Then transported outside the nucleus, and used


as a blueprint for producing new HIV proteins
and enzymes
4. Assembly, Budding and Maturation

• HIV proteins and enzymes gather to form new viral


particles

• HIV Protease cleaves long strands of protein into smaller


pieces, used to construct mature viral cores

• Next structural components assemble to produce a


mature HIV virion

• HIV virus released by budding & spreads quickly through


out the human body
HIV Replication

1. Entry

2. Reverse
Transcription and
Integration

3. Transcription and
Translation

4. Assembly

5. Budding and
Maturation
Transmission

• Sexual route

• Blood / blood product route

• Mother-to-child transmission
HIV Testing
• Those recently exposed should be retested at least six
months after their last exposure
• Screening test (ELISA) vs. confirmatory test (IFA/
Western blot)
ELISA (Reactive)

Repeat ELISA (Reactive)

IFA (Reactive) Western Blot (Reactive)

Positive for HIV Positive for HIV


HIV Testing
ELISA
Test
Negative Positive

No HIV Exposure HIV Exposure Repeat


Low Risk High Risk Positive

Negative Repeat ELISA


Positive Run IFA
Every 3 months
Confirmation
for 1 year

Repeat every
6 months for continued
Indeterminate Negative Positive
High risk behavior

Repeat at Repeat at
End Testing Negative 3 weeks 2-4 months
HIV
+
HIV Antiretroviral Therapy
• Highly Active Antiretroviral Therapy (HAART)

– A Combination Therapy

– When HIV replicates it often makes mistakes, so in


any infected person there are many different strains
of virus

– A produced new strain that can be resistant to the


effects of an one antiretroviral drug

– Taking two or more antiretrovirals at the same time


vastly reduces the rate of resistance develops
• 05 groups of antiviral drugs, each attacks HIV in
a different way

– Nucleoside/Nucleotide Reverse Transcriptase


Inhibitors
– Non-Nucleoside Reverse Transcriptase Inhibitors
– Protease Inhibitors
– Integrase Inhibitors
– Fusion or Entry Inhibitors
Treatment
• There is currently no vaccine or cure for HIV or
AIDS

• Challenge to create an effective vaccine mainly


due to the high genetic variability of the virus

• Some of the vaccine strategies against HIV


currently under investigation
Main prospects of new vaccination strategies

• Delivering HIV proteins as immunogens :-


– Live recombinant viral
– bacterial vectors
– plasmid DNA

• Codon-optimization for expression of viral proteins in mammalian


cells

• Alteration in regulatory elements

• Insertion of cytokine expressing genes and new formulations with


polymers obtain to increase immunogenicity of DNA vaccines

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