THE IMMUNOPATHOGENESIS OF HIV INFECTION

THE HUMAN IMMUNODEFICIENCY VIRUS (HIV) 10359bp DNA gp120 gp41 CD4 binding Membrane fusion

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RECEPTORS AND CO-RECEPTORS I. CD4 is a high affinity receptor for HIV gp120 CD4 CCR5 CCR5 co-receptor on monocytes, macrophages and T cells R5 strain of the virus in initial infection CD4 CXCR4 CXCR4 co-receptor on T cells X4 strain of the virus in initial infection Conformational change of gp120 Conformational change of gp41 MEMBRANE FUSION

MistakesEnzyme 1 Mutation in 10 5 bp Reverse Transcriptase DNA-Polymerase 1 Mutation in 10 8 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 %. Perinatal > intrauterin > breast feeding

HIV-1-SPECIFIC CD4+ HELPER, CD8+ CYTOTOXIC T CELLS AND VIRAL LOAD PROGRESSIVENON-PROGRESSIVE HAART THERAPY PRIOR OR AT THE TIME OF SEROCONVERSION? Zidovudin can protect against transmission to the infant Goulder 1999, Altfeld &Rosenberg 2000