HIV associated pathology

Question 1

Major HIV-1 receptors

Answer 1

• CD4 and CD8

- various chemokine receptors e.g CXCR4 and CCR5 are considered as HIV co-receptors

Question 2

CD4+ helper T lymphocytes

Answer 2

• major routes of multiplication and entry for HIV, apart from monocytes
• infected CD4+ T cells and monocytes which circulate in the blood are the potential source of CNS infection

Question 3

Macrophage-tropism

Answer 3

• strains of HIV which are isolated in the brain have characteristic infecting macrophages rather than lymphocytes
• related to a mutation in a specidic region of gp120, the external glycoprotein of the virus
• in the later stages of the infection, active replication of the virus generates more of these mutants and the compromised immune system permits the escape of these mutants, leading to predominace of macrophage-trophic strains

Question 4

Crossing the blood brain barrier

Answer 4

• in order to enter the brain, HI-1 must cross the BBB using mechanisms that remain unclear
• generally accepted model is the Trojan Horse theory
• HIV enters the CNS as a passenger in ceolls trafficking to thebrain via CD4 T cells or monocytes
• virus accumulation in perivascular regions has been demonstrated as proof

Question 5

Cells infected

Answer 5

• theoretically all the main cell types of the CNS, astrocytes, oligodendrocytes, neurons, perivascular macrophage and microglia can be infected by HIV-1 since they possess the receptors and/or co-receptors for HIV-1 entry
• only the latter two are the most commonly infected cells by HIV-1

Question 6

Neurodegeneration

Answer 6

-infected macrophages and microglia shed viral proteins and release cytokines and neurotoxins into the CNS
-that and TNF alpha contribute to the disruption of the blood brain barrier
-these in turn become more permeable to infected monocytes and cytokines
-secreted cytokines activate microglia and astrocytes which in turn secrete neurotoxins
-

Question 7

Biopsy findings

Answer 7

• infiltration of macrophages into the CNS
• formation of microglial nodules
• multnucleated giant cells from virus induced fusion of microglia and/or macrophages in central white and deep gray matter
• astrocyte activation and damage
• neuronal loss particularly in the hippocampus, basal ganglia and caudate nucleus
• a variable degree of white matter pathology with myelin damage
• accumulation of lipid macrophages in extreme cases

Question 8

Most common psychiatric presentation

Answer 8

• HIV-related dementia
• followed by depresssion
• psychosis is seen in 10% of HIV infected individuals