CD4 and HIV

1
CD4 and HIV
by

• Tan Swee Huang
• AIT UEEM

ED19.98 Bioengineering and Environmental Health
2
Outline

• Life Cycle of HIV
• Major Target Cells for HIV
• Cell surface receptors for HIV
• CD4
• CD4- gp120 Interactions
• Theories of Immune System cell Loss in HIV
  infection
• Challenges Ahead

3
Life Cycle of HIV
Steps in Viral Replication 1. Attachment/Entry 2.
Reverse Transcription DNA Synthesis 3.
Transport to Nucleus 4. Integration 5. Viral
Transcription 6. Viral Protein Synthesis 7.
Assembly of Virus 8. Release of Virus 9.
Maturation
4
Major Target Cells for HIV

• Infection
• CD4 T-Lymphocytes
• CD4 monocytes and macrophages (inclu. microglia)
• CD4 Dendritic cells (inclu. Langerhans cells)

5
Major Target Cells for HIV

• Attachment/Presentation
• Folicular dendritic cells in lymph nodes
• M cells on Peuyers patches
• Galactosylcerebroside positive cells in brain and
  gut

6
Cell surface receptors for HIV (Attachment,
Entry, Fusion)

• CD4 differentiation antigen
• Galactosylcerebroside glycolipid
• LFA-1 Adhesion receptor
• Fc receptors
• Complement receptors
• Proteinases (?)

7
CD4

• Cluster Designation 4
• Expressed on T-helper lymphocytes
• signaling other cells in immune system
• healthy 8001200 CD4 T cells/mm3
• AIDS lt 200 CD4 T cells/mm3
• less densely on macrophages, dendritic cell and
  microglial cells

8
CD4 - gp 120 Interaction

• Virus peptide approaches CD4
• Virus docking
• conformational changes (proteolytic cleavage of
  V3 loop exposes the fudigenc domain of gp41)
• fusion of virion envelope

9
Theories of Immune System cell Loss in HIV
infection

• Direct cell killing
• Syncytia formation
• Apoptosis
• Innocent bystanders
• Anergy
• Superantigens
• Damage to Precursor cells

10
Challenges Ahead

• Role of CD8 T cells
• attack and killed infected cells
• secrete soluble factors that suppress HIV
  replication (e.g. RANTES, MIP-1alpha, MIP-1 beta)
  

11
Challenges Ahead

• Blocking gp 120 binding to CD4
• problem cause hemorrhaging
• Secondary receptor for fusion (fusion
  cofactor/fusin)
• new target for anti-HIV drug (JM3100)
• first true animal model for HIV infection
• not effective on macrophages infection
• function unknown

12
Challenges Ahead

• Antibodies to V3-loop on gp 120
• differ from macrophages to lymphocytes
• 510 patients show no symptoms stable CD4 T
  cell counts
• chemokines(?)
• genetic