THE IMMUNOPATHOGENESIS OF HIV INFECTION

THE HUMAN IMMUNODEFICIENCY VIRUS (HIV)

10359bp DNA10359bp DNA

gp120

gp41

CD4 bindingMembrane fusion

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RECEPTORS AND CO-RECEPTORS I.

CD4 is a high affinity receptor for HIV gp120

CD4CCR5

CCR5 co-receptor on monocytes, macrophages and T cells

R5 strain of the virus in initial infection

CD4CXCR4

CXCR4 co-receptor on T cells

X4 strain of the virus in initial infection

Conformational change of gp120

Conformational change of gp41

MEMBRANE FUSION

MistakesMistakesEnzymeEnzyme

1 Mutation in 101 Mutation in 1055 bp bpReverse TransReverse Transccriptaseriptase

DNA-PolymeraseDNA-Polymerase 1 Mutation in 101 Mutation in 1088 bp bp

THE CAUSE OF HIV VARIABILITY

THE VIRAL REVERSE TRANSCRIPTASE LACKS PROOF READING MECHANISMS OF TYPE POSSESSED BY CELLULAR DNA

NEW VIRAL VARIANTS (quasi species) CO-EXIST IN AN INDIVIDUAL

NEGATIVE SELECTION OF NEUTRALIZING AND CYTOTOXIC EPITOPES

9% of the Caucasian population is heterozygous for a deletion mutant of the CCR5 gene, which results in an unfunctional protein

People homozygous for an inherited defect of the CCR5 gene are resistant to HIV infection – 1% of the Caucasian population

DEPLETION OF CD4+ CELLS IN HIV INFECTION

CD4+ T CELL DEPLETION IN HIV INFECTION

Loss of CD4+ T cells in lymphoid organs

1. Direct cytopathic effect of HIV – lytic cycle in activated CD4+ T cells

2. Killing by virus-specific CD8+ T lymphocytes – CD4+HIV+ targets

3. Uninfected CD4+ T cells bind gp120 – CD4 + TCR signaling apoptosis

4. Syncytia formation – gp120 of infected T binds to uninfected T fusion

5. Inhibited T cell development

THE COURSE OF HIV INFECTION

OPPORTUNISTIC INFECTIONS AND TUMORS

IN HIV INFECTION

KAPOSI SARCOMA AND HERPES SIMPLEX VIRUS INFECTION IN HIV-INFECTED PATIENTS

Candia albicans infection

Three main transmission routes for HIV have been identified

Sexual

The risk of female-to-male transmission is 0.04% per act and male-to-female transmission is 0.08% per act.          

Blood products

Blood transfusion, intravenous drug users, piercings, tattoos                 

Mother-to-child                        The risk of transmission is 20-33 %.

Perinatal > intrauterin > breast feeding                       

HIV-1-SPECIFIC CD4+ HELPER, CD8+ CYTOTOXIC T CELLS AND VIRAL LOAD

PROGRESSIVE NON-PROGRESSIVE

HAART THERAPY

PRIOR OR AT THE TIME OF SEROCONVERSION?

Zidovudin can protect against transmission to the infant

Goulder 1999, Altfeld &Rosenberg 2000