This presentation covers the introduction to HIV and AIDS. The HIV lifecycle is covered to illustrate why the virus is adamant once it infects the human cell.

1. INTRODUCTION TO HIV/AIDS

2. • What is HIV - HIV stands for “Human Immunodeficiency Virus” –
• HIV is a virus that attacks the body’s immune system.
• The immune system protects the body from by producing antibodies
• AIDS- stands for Acute immune deficiency syndrome

3. • The human immunodeficiency virus (HIV) is a retrovirus
belonging to the family of lentiviruses.
• Retroviruses can use their RNA and host DNA to make viral
DNA and are known for their long incubation periods.
• HIV causes severe damage to the immune system and
eventually destroys it by using the DNA of CD4+ cells to
replicate itself.
• Size: 1/10,000th of a millimeter in diameter.

4. • HIV Types-HIV type 1 (HIV-1) and HIV-2.
• HIV-2 appears to progress more slowly.
• Most HIV-2 cases are found in western Africa
• Various subtypes of HIV-1 have been found in specific
geographic areas and in specific high-risk groups

5. • SUBTYPES OF HIV-1
• Subtype A: Central Africa, sub-Saharan Africa
• Subtype B: South America, Brazil, United States, Thailand,
Europe,
Caribbean, India, Japan
• Subtype C: Brazil, India, South Africa
• Subtype D: Central África, sub-Saharan África
• Subtype E: Thailand, Central African Republic, Southeast Asia
• Subtype F: Brazil, Romania, Democratic Republic of Congo

6. • Subtype G: Democratic Republic of Congo, Gabon, Thailand,
Russia,
Central Africa
• Subtype H: Democratic Republic of Congo, Gabon, Russia,
Central Africa
• Subtype I: Cyprus
• Subtype O: Cameroon, Gabon

8. HIV STRUCTURE OF HIV VIRUS

9. • HIV is an enveloped RNA virus: As HIV buds out of the host
cell during replication, it acquires a phospholipid envelope.
• Protruding from the envelope are peg-like structures that the
viral RNA encodes.
• Each peg consists of three or four gp41 glycoproteins (the
stem), capped with three or four gp120 glycoproteins.

10. • Inside the envelope the bullet-shaped nucleocapsid of the
virus is composed of protein and surrounds two single strands
of RNA.
• Three enzymes important to the virus’s life cycle — reverse
transcriptase, integrase, and protease — are also within the
nucleocapsid

11. • Although helper T cells seem to be the main target for HIV,
other cells can become infected as well.
• These include monocytes and macrophages, which can hold
large numbers of viruses within themselves without being killed.
Some T cells harbor similar reservoirs of the virus.

12. • Entry of HIV into the host cell requires the binding of one or
more gp120 molecules on the virus to CD4 molecules on the
host cell’s surface.

13. STRUCTURE OF HIV
• The inner sphere contains :
• Two single-stranded copies of the genomic material, RNA,
• Multiple proteins and enzymes necessary for HIV replication
and maturation: p24, p17, reverse transcriptase, integrase, and
protease.

14. • The three principal genes are gag-capsid proteins, pol-viral
enzymes, and env-envelope proteins.
• The gag gene encodes (provides genetic information) core
proteins.
• The pol gene encodes (provides genetic information) the
enzymes reverse transcriptase, protease, and integrase.
• The env gene encodes (provides genetic information) the HIV
structural components known as glycoproteins.
• The rest of the genes—rev, nef, vif, vpu, vpr, and tat—are
important( regulatory) for viral replication and enhancing HIV’s
infectivity rate.

15. • gag- group specific antigen
• pol- polymerase
• env- envelope
• rev- transactivating protein for HIV -1 regulation
• nef- negative regulatory factor
• vif- viral infectivity factor
• vpu- virus protein u
• vpr- lentivirus protein R
• tat- transactivator of transcription

16. • Host cells infected with HIV have a shortened life span as a
result of the virus using them as “factories” to produce multiple
copies of new HIV.
• Thus, HIV continuously uses new host cells to replicate
itself. As many as 10 million to 10 billion virions (individual
viruses) are produced daily.
• In the first 24 hrs after exposure, HIV attacks or is captured by
dendritic cells ( antigen presenting cells) in the mucous
membranes and skin.

17. HIV’S LIFE CYCLE
• Within 5 days after exposure, these infected cells make their
way to the lymph nodes and eventually to the peripheral blood,
where viral replication becomes rapid
• CD4+ lymphocytes that are recruited to respond to viral antigen
migrate to the lymph nodes.
• These(CD4+) become activated and then proliferate via
complex interaction of cytokines released in the
microenvironment of the lymph nodes.

18. • This sequence of events makes the CD4+ cells more
susceptible to HIV infection,.
• It also explains the generalized lymphadenopathy characteristic
of the acute retroviral syndrome seen in adults and adolescents.
• In contrast, HIV-infected monocytes allow viral replication but
resist killing.
• Thus, monocytes act as reservoirs of HIV and as effectors of
tissue damage in organs such as the brain.

19. HIV LIFE CYCLE
• The seven stages of the HIV life cycle are:
• Binding
• Fusion
• Reverse Transcription
• Integration
• Replication
• Assembly
• Budding and maturation

20. • 1 & 2. Binding And Fusion
• The envelope proteins gp120 and gp41 bind to CD4+ cell
receptors and co receptors on the outside of CD4+ cells and
macrophages.
• The chemokine co-receptors CCR5 and CXCR4 facilitate viral
entry.
• T-cell tropic(many cells & tissues) viruses require CXCR4 to
bind, and macrotropic ( macrophages) strains of the virus
require CCR5.

21. • The joining of the proteins and the receptors and co receptors
fuses the HIV membrane with the CD4+ cell membrane, and
the virus enters the CD4+ cell and macrophage.
• The HIV membrane and the envelope proteins remain outside
of the CD4+ cell, whereas the core of the virus enters the
CD4+ cell.
• CD4+ cell enzymes interact with the viral core and stimulate
the release of viral RNA and the viral enzymes reverse
transcriptase, integrase, and protease.

22. Binding and FUSION ct,

23. • Reverse Transcription
• The HIV RNA must be converted to DNA before it can be
incorporated into the DNA of the CD4+ cell.
• This incorporation must occur for the virus to multiply.
• HIV RNA is converted to single strand of HIV DNA by the help
of HIV enzyme reverse transcriptase.
• The single strand of this new DNA then undergoes replication
into double-stranded HIV DNA.

25. • Integration
• Once reverse transcription has occurred:
• The viral DNA enters the nucleus of the CD4+ cell and
finally its inserted into the CD4+ cell’s DNA ( a process
called integration) by the viral enzyme integrase
• At this level ,the CD4+ cell has now been changed into a
factory used to produce more HIV.

27. • Replication
• Once integrated into the CD4 DNA, the HIV begin to use the
machinery of the CD4 cell make long chains of HIV proteins
which are the building blocks for more HIV.
• Provirus (HIV DNA) is replicated along with the chromosome
when the cell divides.
• The integration of provirus into the host DNA provides the
latency that enables the virus to evade host responses so
effectively.

28. • Assembly
• The HIV proteins and viral RNA, all the components needed to
make a new virus, gather /assemble at the CD4+ cell
membrane to form new viruses.
• Production of viral proteins and RNA takes place when the
provirus is transcribed. Viral proteins are then assembled
using the host cell’s protein-making machinery.
• The virus’s protease enzyme allows for the processing of
newly translated polypeptides into the proteins, which are then
ultimately assembled into viral particles.

29. • These new viruses leave the CD4+ cell and contain all the
components necessary to infect other CD4+ cells but cannot
do so until it has matured.
• During this process, the HIV protease enzyme cuts the long HIV
proteins of the virus into smaller functional units that then
reassemble to form a mature virus.
• The virus is now ready to infect other cells.

30. • Budding and Maturation
• These new immature viruses push through the different parts of
the cell wall by budding.
• Many viruses can push through the wall of one CD4+ cell. The
virus eventually buds out of the cell.
• A cell infected with a retrovirus does not necessarily lyse
the cell when viral replication takes place; rather, many viral
particles can bud out of a cell over the course of time.

33. • VIDEO AVAILABLE ON HIV LIFECYCLE

34. • Effects on the Immune System
• The HIV viral burden directly and indirectly mediates CD4+ T-
cell destruction.
• There is destruction of mature CD4+ cells;
• CD4+ progenitor cells in bone marrow, the thymus, and peripheral
lymphoid organs; as well as CD4+ cells within the nervous system, such
as microglia.
• The result of this destruction is failure of T-cell production and
eventual immune suppression.

35. • HIV Virus Load
• HIV is an RNA virus  HIV RNA is what is detected in blood
• P24 antigen can be detected early in HIV infection, before antibodies
(6 – 8 wks after)
• “Undetectable”: <50 copies/ml

36. • What are CD4 T Cells?
• Play important role in immune response of healthy individual
• Activate B cells which produce antibodies
• Stages of CD4 cell count in HIV infection
• Before HIV infection: 800 – 1000/mm3
• Sero-conversion illness: ~500/mm3
• Adaptive immune response: ~700/mm3
• AIDS: <200/mm3

38. STAGES OF A TYPICAL HIV INFECTION BY CDC

39. • REVISION QUESTIONS
• Differentiate between HIV & AIDS
• State two types of HIV, HIV -1 Subtypes.
• With the aid of a diagram, explain the structure of HIV
• Explain the life cycle of HIV
• What is the effect of HIV to the body’s immune system