Infection of primary human microglia and monocyte-derived macrophages with human immunodeficiency virus type 1 isolates: evidence of differential tropism.
Julie M. Strizki,Andrew V. Albright,Hai Sheng,Michael J. O'Connor,Luc Perrin,Francisco Gonzalez-Scarano +5 more
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TLDR
The hypothesis that HIV-1 infection can be established in the central nervous system by viruses present early in HIV infection, that some of these viruses are particularly tropic for microglia, and that adaptation in this cell type can result in the selection of a pool of predominantlymicroglia-tropic (neurotropic) viruses are supported.Abstract:
To ascertain whether viruses present at the time of primary viremia can infect the central nervous system and to determine if microglial tropism is distinct from tropism for monocyte-derived macrophages (MDM), 27 human immunodeficiency virus type 1 (HIV-1) isolates obtained from acutely infected individuals, as well as laboratory strains, were assayed for their ability to replicate in primary adult microglial cultures and in MDM. Most of the isolates replicated equally well in both microglia and MDM, but several isolates replicated preferentially in one of the two cell types, differing by as much as 40-fold in p24gag production. This indicated that while MDM and microglial tropism overlap, a subset of isolates is particularly tropic for one of the two cell types. One isolate was further adapted to microglia by 15 sequential passages, raising the peak p24 concentration produced by 1,000-fold. In addition, the passaged virus induced marked cytopathologic changes (vacuolization and syncytium formation) in infected microglial cultures. Sequence comparison of the V3 loop of unpassaged and multiply passaged virus revealed amino acid changes shown to be associated with isolates from patients with HIV dementia. Our data support the hypothesis that HIV-1 infection can be established in the central nervous system by viruses present early in HIV infection, that some of these viruses are particularly tropic for microglia, and that adaptation in this cell type can result in the selection of a pool of predominantly microglia-tropic (neurotropic) viruses.read more
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The neuropathogenesis of AIDS
TL;DR: The studies that are being carried out to determine the respective contributions of infection, and monocyte and macrophage activation, to disease progression are discussed.
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Microglia as mediators of inflammatory and degenerative diseases.
TL;DR: The role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease is discussed in this article, where the authors discuss their role in protecting the central nervous system.
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CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia
Jianglin He,Youzhi Chen,Michael Farzan,Hyeryun Choe,Asa Ohagen,Suzanne Gartner,Jorge Busciglio,Jorge Busciglio,Xiaoyu Yang,Wolfgang Hofmann,Walter Newman,Charles R. Mackay,Joseph Sodroski,Dana Gabuzda +13 more
TL;DR: The CCR3 ligand, eotaxin, and an anti-CCR3 antibody inhibited HIV-1 infection of microglia, as did MIP-1β, which is a CCR5 ligand that promotes efficient infection of the CNS by HIV- 1.
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Perivascular Macrophages Are the Primary Cell Type Productively Infected by Simian Immunodeficiency Virus in the Brains of Macaques: Implications for the Neuropathogenesis of AIDS
Kenneth C. Williams,Sarah Corey,Susan V. Westmoreland,Doug Pauley,Heather Knight,Colin D. deBakker,Xavier Alvarez,Andrew A. Lackner +7 more
TL;DR: The biology of perivascular macrophages, including their rate of turnover and replacement by peripheral blood monocytes, may explain the timing of neuroinvasion, disappearance, and reappearance of virus in the CNS, and questions the ability of the brain to function as a reservoir for productive infection by HIV/SIV.
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Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus.
TL;DR: Key features of HIV-1-cell interactions in the CNS are reviewed and their contributions to persistence and pathogenicity of AIDS-related illnesses in individuals without AIDS are reviewed.
References
More filters
Journal ArticleDOI
Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy.
Scott Koenig,Howard E. Gendelman,Jan M. Orenstein,Mauro C. Dal Canto,Gholam H. Pezeshkpour,Margaret Yungbluth,Frank Janotta,Allen J. Aksamit,Malcolm A. Martin,Anthony S. Fauci +9 more
TL;DR: The identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals and these cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients.
Journal ArticleDOI
Genotypic and phenotypic characterization of HIV-1 patients with primary infection
TL;DR: In five HIV-1 seroconverters, the viral phenotype was found to be uniformly macrophage-tropic and non-syncytium-inducing and the viruses were genotypically homogeneous within each patient, but a common signature sequence was not discernible among transmitted viruses.
Journal ArticleDOI
The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex
Richard W. Price,Bruce J. Brew,John J. Sidtis,Marc K. Rosenblum,Adrienne C. Scheck,Paul D. Cleary +5 more
TL;DR: Within the context of the permissive effect of immunosuppression, genetic changes in HIV-1 may underlie the neuropathological heterogeneity of the AIDS dementia complex and its relatively independent course in relation to the systemic manifestations of AIDS noted in some patients.
Journal ArticleDOI
Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients
TL;DR: The brains of 12 AIDS patients were studied using in situ hybridization to identify human immunodeficiency virus nucleic acid sequences and immunocytochemistry to identify viral and cellular proteins, suggesting that CNS dysfunction is due to indirect effects rather than neuronal or glial infection.
Journal ArticleDOI
High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection.
Stephen J. Clark,Michael S. Saag,W. Don Decker,Sherri Campbell-Hill,Joseph L. Roberson,Peter J. Veldkamp,John C. Kappes,Beatrice H. Hahn,George M. Shaw +8 more
TL;DR: Primary, symptomatic HIV-1 infection is associated with high titers of cytopathic, replication-competent viral strains, and during such infection potential infectivity is enhanced.