Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients

C. Power, Justin Charles McArthur, A. Nath, K. Wehrly, M. Mayne, J. Nishio, T. Langelier, Richard Johnson, B. Chesebro

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection of the brain results in viral replication primarily in macrophages and microglia. Despite frequent detection of viral genome and proteins in the brains of AIDS patients with and without HIV dementia, only 20% of AIDS patients become demented. To investigate the role of viral envelope gene variation in the occurrence of dementia, we examined regions of variability in the vital envelope gene isolated from brains of AIDS patients. Brain-derived HIV-1 V1- V2 envelope sequences from seven demented and six nondemented AIDS patients displayed significant sequence differences between clinical groups, and by phylogenetic analysis, sequences from the demented group showed clustering. Infectious recombinant viruses containing brain-derived V3 sequences from both clinical groups were macrophagetropic, and viruses containing brain- derived V1, V2, and V3 sequences from both clinical groups spread efficiently in macrophages. In an indirect in vitro neurotoxicity assay using supernatant fluid from HIV-1-infected macrophages, recombinant viruses from demented patients induced greater neuronal death than viruses from nondemented patients. Thus, the HIV-1 envelope diversity observed in these patient groups appeared to influence the release of neurotoxic molecules from macrophages and might account in part for the variability in occurrence of dementia in AIDS patients.

Original languageEnglish (US)
Pages (from-to)9045-9053
Number of pages9
JournalJournal of Virology
Volume72
Issue number11
StatePublished - Nov 1998

Fingerprint

Brain Death
Human immunodeficiency virus 1
HIV-1
Acquired Immunodeficiency Syndrome
death
brain
Genes
dementia
Brain
macrophages
genes
Macrophages
Viruses
viruses
Dementia
AIDS Dementia Complex
neurotoxicity
Viral Genes
Viral Genome
neuroglia

ASJC Scopus subject areas

  • Immunology

Cite this

Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients. / Power, C.; McArthur, Justin Charles; Nath, A.; Wehrly, K.; Mayne, M.; Nishio, J.; Langelier, T.; Johnson, Richard; Chesebro, B.

In: Journal of Virology, Vol. 72, No. 11, 11.1998, p. 9045-9053.

Research output: Contribution to journalArticle

@article{e3fece327ee14b39b97560291a0d2229,
title = "Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients",
abstract = "Human immunodeficiency virus type 1 (HIV-1) infection of the brain results in viral replication primarily in macrophages and microglia. Despite frequent detection of viral genome and proteins in the brains of AIDS patients with and without HIV dementia, only 20{\%} of AIDS patients become demented. To investigate the role of viral envelope gene variation in the occurrence of dementia, we examined regions of variability in the vital envelope gene isolated from brains of AIDS patients. Brain-derived HIV-1 V1- V2 envelope sequences from seven demented and six nondemented AIDS patients displayed significant sequence differences between clinical groups, and by phylogenetic analysis, sequences from the demented group showed clustering. Infectious recombinant viruses containing brain-derived V3 sequences from both clinical groups were macrophagetropic, and viruses containing brain- derived V1, V2, and V3 sequences from both clinical groups spread efficiently in macrophages. In an indirect in vitro neurotoxicity assay using supernatant fluid from HIV-1-infected macrophages, recombinant viruses from demented patients induced greater neuronal death than viruses from nondemented patients. Thus, the HIV-1 envelope diversity observed in these patient groups appeared to influence the release of neurotoxic molecules from macrophages and might account in part for the variability in occurrence of dementia in AIDS patients.",
author = "C. Power and McArthur, {Justin Charles} and A. Nath and K. Wehrly and M. Mayne and J. Nishio and T. Langelier and Richard Johnson and B. Chesebro",
year = "1998",
month = "11",
language = "English (US)",
volume = "72",
pages = "9045--9053",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients

AU - Power, C.

AU - McArthur, Justin Charles

AU - Nath, A.

AU - Wehrly, K.

AU - Mayne, M.

AU - Nishio, J.

AU - Langelier, T.

AU - Johnson, Richard

AU - Chesebro, B.

PY - 1998/11

Y1 - 1998/11

N2 - Human immunodeficiency virus type 1 (HIV-1) infection of the brain results in viral replication primarily in macrophages and microglia. Despite frequent detection of viral genome and proteins in the brains of AIDS patients with and without HIV dementia, only 20% of AIDS patients become demented. To investigate the role of viral envelope gene variation in the occurrence of dementia, we examined regions of variability in the vital envelope gene isolated from brains of AIDS patients. Brain-derived HIV-1 V1- V2 envelope sequences from seven demented and six nondemented AIDS patients displayed significant sequence differences between clinical groups, and by phylogenetic analysis, sequences from the demented group showed clustering. Infectious recombinant viruses containing brain-derived V3 sequences from both clinical groups were macrophagetropic, and viruses containing brain- derived V1, V2, and V3 sequences from both clinical groups spread efficiently in macrophages. In an indirect in vitro neurotoxicity assay using supernatant fluid from HIV-1-infected macrophages, recombinant viruses from demented patients induced greater neuronal death than viruses from nondemented patients. Thus, the HIV-1 envelope diversity observed in these patient groups appeared to influence the release of neurotoxic molecules from macrophages and might account in part for the variability in occurrence of dementia in AIDS patients.

AB - Human immunodeficiency virus type 1 (HIV-1) infection of the brain results in viral replication primarily in macrophages and microglia. Despite frequent detection of viral genome and proteins in the brains of AIDS patients with and without HIV dementia, only 20% of AIDS patients become demented. To investigate the role of viral envelope gene variation in the occurrence of dementia, we examined regions of variability in the vital envelope gene isolated from brains of AIDS patients. Brain-derived HIV-1 V1- V2 envelope sequences from seven demented and six nondemented AIDS patients displayed significant sequence differences between clinical groups, and by phylogenetic analysis, sequences from the demented group showed clustering. Infectious recombinant viruses containing brain-derived V3 sequences from both clinical groups were macrophagetropic, and viruses containing brain- derived V1, V2, and V3 sequences from both clinical groups spread efficiently in macrophages. In an indirect in vitro neurotoxicity assay using supernatant fluid from HIV-1-infected macrophages, recombinant viruses from demented patients induced greater neuronal death than viruses from nondemented patients. Thus, the HIV-1 envelope diversity observed in these patient groups appeared to influence the release of neurotoxic molecules from macrophages and might account in part for the variability in occurrence of dementia in AIDS patients.

UR - http://www.scopus.com/inward/record.url?scp=0031690759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031690759&partnerID=8YFLogxK

M3 - Article

C2 - 9765449

AN - SCOPUS:0031690759

VL - 72

SP - 9045

EP - 9053

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 11

ER -