Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS

Anne Valérie Vallat, Umberto De Girolami, Johnny Jianglin He, Abner Mhashilkar, Wayne Marasco, Bin Shi, Françoise Gray, Jeanne Bell, Catherine Keohane, Thomas W. Smith, Dana Gabuzda

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

The chemokine receptors CCR5 and CXCR4 are coreceptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage- tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV- 1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4- positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

Original languageEnglish
Pages (from-to)167-178
Number of pages12
JournalAmerican Journal of Pathology
Volume152
Issue number1
StatePublished - 1 Jan 1998

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CCR5 Receptors
CXCR4 Receptors
HIV-1
Acquired Immunodeficiency Syndrome
Brain
Macrophages
Microglia
Encephalitis
Viruses
Virus Internalization
Chemokine Receptors
Brain Diseases
Virus Diseases
Virus Replication
Disease Progression
Autopsy
Central Nervous System
Pediatrics
Neurons
Cell Line

Cite this

Vallat, A. V., De Girolami, U., He, J. J., Mhashilkar, A., Marasco, W., Shi, B., ... Gabuzda, D. (1998). Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS. American Journal of Pathology, 152(1), 167-178.
Vallat, Anne Valérie ; De Girolami, Umberto ; He, Johnny Jianglin ; Mhashilkar, Abner ; Marasco, Wayne ; Shi, Bin ; Gray, Françoise ; Bell, Jeanne ; Keohane, Catherine ; Smith, Thomas W. ; Gabuzda, Dana. / Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS. In: American Journal of Pathology. 1998 ; Vol. 152, No. 1. pp. 167-178.
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Vallat, AV, De Girolami, U, He, JJ, Mhashilkar, A, Marasco, W, Shi, B, Gray, F, Bell, J, Keohane, C, Smith, TW & Gabuzda, D 1998, 'Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS', American Journal of Pathology, vol. 152, no. 1, pp. 167-178.

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS. / Vallat, Anne Valérie; De Girolami, Umberto; He, Johnny Jianglin; Mhashilkar, Abner; Marasco, Wayne; Shi, Bin; Gray, Françoise; Bell, Jeanne; Keohane, Catherine; Smith, Thomas W.; Gabuzda, Dana.

In: American Journal of Pathology, Vol. 152, No. 1, 01.01.1998, p. 167-178.

Research output: Contribution to journalArticle

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AU - Vallat, Anne Valérie

AU - De Girolami, Umberto

AU - He, Johnny Jianglin

AU - Mhashilkar, Abner

AU - Marasco, Wayne

AU - Shi, Bin

AU - Gray, Françoise

AU - Bell, Jeanne

AU - Keohane, Catherine

AU - Smith, Thomas W.

AU - Gabuzda, Dana

PY - 1998/1/1

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N2 - The chemokine receptors CCR5 and CXCR4 are coreceptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage- tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV- 1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4- positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

AB - The chemokine receptors CCR5 and CXCR4 are coreceptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage- tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV- 1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4- positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

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Vallat AV, De Girolami U, He JJ, Mhashilkar A, Marasco W, Shi B et al. Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS. American Journal of Pathology. 1998 Jan 1;152(1):167-178.