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The new face of AIDS Science 272, 1996, 1855, 1880-81, 1884
Costs (or profit) of HIV  Science 272, 1996, 1855, 1880-81, 1884 <ul><li>Diagnostics </li></ul><ul><ul><li>ELISA </li></ul...
ELISA <ul><li>HIV- or HIV-protein  coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li><...
ELISA <ul><li>HIV- or HIV-protein  coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li><...
ELISA <ul><li>HIV- or HIV-protein  coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li><...
ELISA <ul><li>HIV- or HIV-protein  coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li><...
ELISA <ul><li>HIV- or HIV-protein  coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li><...
PCR: polymerase chain reaction a way to amplify the amount of DNA <ul><li>From ng (10 -9  gram) to µg (10 -6  g) in a few ...
Mechanism of protease inhibitor  Science 272, 1996, 1855, 1880-81, 1884 <ul><li>Dimer </li></ul><ul><li>Ritonavir (green b...
Typical course of an HIV-infection Science 272, 1996, 1855, 1880-81, 1884 <ul><li>Setpoint: lowest HIV viral load (RNA cop...
T-cell responses during HAART Altfeld et al., 2002, Nature 420, 434-439 <ul><li>During HAART: low viral load    low immun...
T-cell responses during HAART Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Viral load (VL) increase during interrupti...
T-cell response during STI  Altfeld et al., 2002, Nature 420, 434-439 <ul><li>STI: supervised treatment interruption </li>...
Sequence of patient’s HIV  Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Grey box: CD8 epitope </li></ul><ul><li>Antig...
Phylogenetic tree of gag-sequence  Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Compare days 18 and 131 with days 102...
PCR analysis of viruses  Altfeld et al., 2002, Nature 420, 434-439 <ul><li>In this PCR, RNA is first converted into DNA, t...
T-cell responses during HAART Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Superinfection: secondary infection </li><...
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GKA deel 2 college 11

  1. 1. The new face of AIDS Science 272, 1996, 1855, 1880-81, 1884
  2. 2. Costs (or profit) of HIV Science 272, 1996, 1855, 1880-81, 1884 <ul><li>Diagnostics </li></ul><ul><ul><li>ELISA </li></ul></ul><ul><ul><ul><li>Seropositive </li></ul></ul></ul><ul><ul><ul><li>Incubation time </li></ul></ul></ul><ul><ul><li>Western blot </li></ul></ul><ul><li>Monitoring </li></ul><ul><ul><li>CD4-count </li></ul></ul><ul><ul><li>Viral load: PCR </li></ul></ul><ul><li>Vaccins…… </li></ul><ul><li>HAART </li></ul><ul><ul><li>NRTIs </li></ul></ul><ul><ul><li>NNRTIs </li></ul></ul><ul><ul><li>protease inhibitors </li></ul></ul>
  3. 3. ELISA <ul><li>HIV- or HIV-protein coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li></ul><ul><li>Develop with chromogenic substrate </li></ul><ul><li>Colour arises when positive </li></ul>HIV Add serum
  4. 4. ELISA <ul><li>HIV- or HIV-protein coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li></ul><ul><li>Develop with chromogenic substrate </li></ul><ul><li>Colour arises when positive </li></ul>HIV Add serum
  5. 5. ELISA <ul><li>HIV- or HIV-protein coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li></ul><ul><li>Develop with chromogenic substrate </li></ul><ul><li>Colour arises when positive </li></ul>HIV Add serum Add anti-Ig-enzyme
  6. 6. ELISA <ul><li>HIV- or HIV-protein coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li></ul><ul><li>Develop with chromogenic substrate </li></ul><ul><li>Colour arises when positive </li></ul>HIV Add serum Add anti-Ig-enzyme Add substrate
  7. 7. ELISA <ul><li>HIV- or HIV-protein coated plastic plate </li></ul><ul><li>Add serum </li></ul><ul><li>Add conjugate </li></ul><ul><li>Develop with chromogenic substrate </li></ul><ul><li>Colour arises when positive </li></ul>HIV Add serum Add anti-Ig-enzyme Add substrate
  8. 8. PCR: polymerase chain reaction a way to amplify the amount of DNA <ul><li>From ng (10 -9 gram) to µg (10 -6 g) in a few hours </li></ul><ul><ul><li>Kary Mullen </li></ul></ul><ul><ul><li>Heat-stable DNA polymerase </li></ul></ul>
  9. 9. Mechanism of protease inhibitor Science 272, 1996, 1855, 1880-81, 1884 <ul><li>Dimer </li></ul><ul><li>Ritonavir (green balls) blocks active site </li></ul><ul><li>Active site very hydrophobic (LKLMMGIAVIL) </li></ul><ul><ul><li>Very difficult with orally taken drugs </li></ul></ul>
  10. 10. Typical course of an HIV-infection Science 272, 1996, 1855, 1880-81, 1884 <ul><li>Setpoint: lowest HIV viral load (RNA copies per mL) </li></ul><ul><ul><li>benefit  treat early?? </li></ul></ul><ul><li>Breakpoint: surrender of immune system </li></ul><ul><ul><li>increase of viral load </li></ul></ul><ul><ul><li>decrease of CD4 </li></ul></ul>==============
  11. 11. T-cell responses during HAART Altfeld et al., 2002, Nature 420, 434-439 <ul><li>During HAART: low viral load  low immune response </li></ul><ul><li>Supervised treatment interruption: STI </li></ul><ul><ul><li>Patient care </li></ul></ul><ul><ul><li>Induction immune system </li></ul></ul><ul><li>Patient had 25 CTL clones against viral proteins </li></ul>
  12. 12. T-cell responses during HAART Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Viral load (VL) increase during interruption </li></ul><ul><li>After 1000 days, VL rises to 500,000/mL </li></ul><ul><ul><li>(1 mm 3 = 1 ??L?) </li></ul></ul>
  13. 13. T-cell response during STI Altfeld et al., 2002, Nature 420, 434-439 <ul><li>STI: supervised treatment interruption </li></ul><ul><li>SFC: measure of CTL efficiency </li></ul><ul><li>PBMC: peripheral blood mononuclear cells </li></ul>
  14. 14. Sequence of patient’s HIV Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Grey box: CD8 epitope </li></ul><ul><li>Antigen processing may be influenced by mutations, in or near T-cell epitope </li></ul>
  15. 15. Phylogenetic tree of gag-sequence Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Compare days 18 and 131 with days 1021 and 1170 </li></ul><ul><li>Your conclusion? </li></ul><ul><li> two distinct viruses </li></ul><ul><li> two times infected </li></ul>
  16. 16. PCR analysis of viruses Altfeld et al., 2002, Nature 420, 434-439 <ul><li>In this PCR, RNA is first converted into DNA, then DNA is amplified, and analyzed via agarose electrophoresis </li></ul><ul><li>Virus A and B belong to clade (=isotype) B </li></ul>Clade B consensus primers Virus A specific primers Virus B specific primers Day 1000 Day 1000 <ul><li>Around day 1000, infection with virus B </li></ul>
  17. 17. T-cell responses during HAART Altfeld et al., 2002, Nature 420, 434-439 <ul><li>Superinfection: secondary infection </li></ul><ul><ul><li>No control by immune system </li></ul></ul><ul><ul><li>VL increased, CD4 decreased </li></ul></ul><ul><ul><li>In spite of strong immune response </li></ul></ul><ul><li>Conclusions for vaccine development? </li></ul><ul><li>Is immune system same for infected, or vaccinated persons? </li></ul><ul><li>Was patient unique? </li></ul>===============

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