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The Body’s Defense Against HIV-Type 1 Infection, Viral Load, and Antigenic Diversity. Emmanuel Jean-Jacques Seminar 475 Dr. Peter Lin. Progression of AIDS. Most individuals infected with HIV remain disease free for many years.

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the body s defense against hiv type 1 infection viral load and antigenic diversity

The Body’s Defense Against HIV-Type 1 Infection, Viral Load, and Antigenic Diversity

Emmanuel Jean-Jacques

Seminar 475

Dr. Peter Lin

progression of aids
Progression of AIDS
  • Most individuals infected with HIV remain disease free for many years.
  • During this time, individuals develop antibodies and cytokines, maintain stable numbers of CD4+ cells, maintain strong Cytotoxic T cell (CTL) responses, and contain low virus load.
  • At some point, the immune system fails and most infected individuals progress the symptoms of AIDS.
why does the immune system fails
Why Does the Immune System Fails?
  • The interaction between HIV and other opportunistic infections
  • Antigenic diversity is at a high level
  • Differences in viral pathogenicity contributing to the development of AIDS
  • Drug-resistant viruses
the correlation of hiv 1 and cd4 receptor
The Correlation of HIV-1 and CD4 Receptor
  • CD4 receptor is part of the membrane of T-cells.
  • During HIV invasion, the gp120 proteins on the surface of the HIV bind to the CD4 receptors
  • Fusion of the virus membrane to the immune cell’s lipid membrane occurs and the contents of the virus particle enter the T-cell. So the cell is now infected.
devising treatments for aids
Devising Treatments for AIDS
  • Because of the unique component (gp120) of HIV. Scientists are trying to devise treatments for AIDS. Recently Scientists have tried to attack the virus before it infects the cells by blocking the gp120 proteins to the CD4 receptor
the development of neutralizing antibody response during hiv 1 infection
The Development of Neutralizing Antibody Response During HIV-1 Infection
  • Basically, this means the ability of the immune system to inhibit virus replication by producing antibodies against the virus’ p24 and gp41 antigens (seroconversion).
  • This humoral response to these antigens produces a high titer of antibody response to the gp120 region of the virus.
humoral response continued
Humoral Response Continued
  • According to this study, HIV-1 causes a primary infection stage that is associated with low seroconversion due to high virus load. The individual who is infected has a series of influenza-like symptoms.
the difference between ccr 5 and cxcr 4 receptors
The Difference Between CCR-5 and CXCR-4 Receptors
  • In the past, HIV isolates have been classified according to the ability to induce cytopathic effects and have veen designated syncytium inducing (SI) or non-syncytium inducing (NSI).
  • SI viruses are able to utilize the -chemokine receptor CXCR-4, which is expressed on naive T cells.
ccr 5 and cxcr 4 receptors continued
CCR-5 and CXCR-4 Receptors Continued
  • NSI viruses utilize only members of the -chemokine receptor CCR-5, which is expressed on memory T cells.
  • Now a days viruses are classified according the co-receptor they utilize.
  • So that means that if CCR-5 were absent from CD4 T cells or even distorted then the virus would not be able to infect the cell.
materials and methods development of neutralizing antibody response to hiv 1
Materials and MethodsDevelopment of Neutralizing Antibody Response to HIV-1
  • A patient (HL60) with influenza-like symptoms was screened for HIV infection by use of four available tests for the detection of HIV-specific antibodies:
    • Cloning and expression of gp120 regions from the seroconversion samples.
    • Antigenic characterization of gp120 proteins.
    • Generation and Recovery of chimeric. HXB2.gp120 viruses.
    • Virus neutralization assays.
cloning and expression of gp120 regions from seroconversion
Cloning and expression of gp120 regions from seroconversion
  • Total RNA was extracted from plasma samples, and the gp120 Open Reading Frame (ORFs) were amplified using RT-PCR.
  • The gp120 ORFs were sequenced with primers.
  • Amino acid numbering was based on the HXB2 gp120 sequence.
results
Results
  • Monitoring the seroconversion process
antigenic characterization of gp120 proteins
Antigenic Characterization of gp120 proteins
  • Soluble gp120 proteins taken from patient (HL60) sera were tested for their ability to bind a pool of :
    • HIV-positive human sera
    • soluble CD4-Immunoglobulin (sCD4-Ig)
    • monoclonal antibodies
results15
Results
  • Antigenic characterization of gp120 proteins
generation and recovery of chimeric hxb2 gp120 viruses
Generation and Recovery of chimeric HXB2.gp120 viruses
  • Three of the virus clones (pCDNA3) from the previous test expressing gp120 and capable of binding sCD4-Ig were chosen for transfer into pHXB2-MCS vector.
  • These vectors were transfected into HEK cells (cocultured with PHA-stimulated peripheral blood lymphocytes (PBL)).
  • The viruses were used to infect U87.CD4 cells that expressed a range of chemokine receptors and antibodies to p24 antigens.
results17
Results
  • Generation and recovery of chimeric HXB2.gp120 viruses
conclusion
Conclusion
  • The results obtained from patient (HL60) demonstrated seroconversion deficiency, meaning that the patient did not produce enough antibodies to the increased viral load.
  • But after 48 hours, during days 11, 12, and 13 there was a reduction in viral load, thus indicating a relative immune response to the virus and potent neutralization of the infection.
  • And there was a limited number in viral antigenic diversity during seroconversion.