Human Immunodeficiency Virus (HIV) Infection in Brains with AIDS-Related Leukoencephalopathy

Rostad, Steve W.; Sumi, S. M.; Shaw, Cheng‐Mei; Olson, Kristin; McDougall, James K.

doi:10.1089/aid.1987.3.363

Cited by 50 publications

(24 citation statements)

References 20 publications

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“…In the rhesus macaque simian immunodeficiency virus (SIV) model, both neurotropic and neurovirulent SIV MAC variants have been described (11,22,38). It is therefore suspected that specific neurotropic and neurovirulent HIV-1 variants exist and are associated with dementia.CCR5-using HIV-1 strains are predominant in the brain (13), and CCR5 ϩ perivascular macrophages and microglia are the cell types most frequently infected (19,35,37,43,49,50). The role of other cell types resident in the brain is less clear.…”

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confidence: 99%

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Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages

Peters

Bhattacharya

Hibbitts

et al. 2004

J Virol

184

282

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Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4 ؉ CCR5 ؉ cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several wellcharacterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophagetropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.Human immunodeficiency virus type 1 (HIV-1) replication in the brain results in the development of severe neurological disorders known as AIDS dementia complex in about 30% of AIDS patients (29). The mechanisms that cause the loss of up to 40% of neurons (10) as well as result in dementia are unclear. In the rhesus macaque simian immunodeficiency virus (SIV) model, both neurotropic and neurovirulent SIV MAC variants have been described (11,22,38). It is therefore suspected that specific neurotropic and neurovirulent HIV-1 variants exist and are associated with dementia.CCR5-using HIV-1 strains are predominant in the brain (13), and CCR5 ϩ perivascular macrophages and microglia are the cell types most frequently infected (19,35,37,43,49,50). The role of other cell types resident in the brain is less clear. There is evidence that CD4Ϫ astrocytes become infected, particularly in pediatric AIDS cases (32,36,37,43). Astrocyte infection is relatively unproductive with early HIV mRNAs (e.g., for rev and nef) detectable, but no late mRNAs encoding the structural gag and env proteins needed to produce progeny virus par...

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confidence: 99%

“…CCR5-using HIV-1 strains are predominant in the brain (13), and CCR5 ϩ perivascular macrophages and microglia are the cell types most frequently infected (19,35,37,43,49,50). The role of other cell types resident in the brain is less clear.…”

mentioning

confidence: 99%

Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages

Peters

Bhattacharya

Hibbitts

et al. 2004

J Virol

184

282

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“…Several early reports demonstrated HIV RNA or proteins in brain endothelial cells in autopsy material from patients with AIDS dementia but this ®nding has not been universal (Kure et al, 1990;Rostad et al, 1987;Smith et al, 1990;Wiley et al, 1986). Moses et al have demonstrated productive infection of cultured human brain microvessel endothelial cells by HIV-1 (Moses et al, 1996.…”

Section: Viral Contributions To Aids Dementiamentioning

confidence: 99%

SIV infection of macaques - modeling the progression to AIDS dementia

Zink¹,

Spelman²,

Robinson³

et al. 1998

J Neurovirol

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AIDS dementia complex affects 15 ± 20% of HIV-infected adults and a greater percentage of HIV-infected children. Whether or not an HIV-infected individual develops neurological disease and how early in infection the clinical signs appear is most likely the net result of both viral virulence factors and host factors. Important viral factors include cell tropism and sequences that determine neurovirulence. The host factors include the cellular expression of viral co-receptors and maintenance of competent immune responses. The pathogenesis of AIDS dementia complex is dif®cult to study in the human host because of the dif®culty in identifying acutely infected individuals and the inaccessibility of human brain tissue for examination during infection. The SIV/ macaque model is excellent for the study of viral virulence factors and host responses to infection. This review outlines how the SIV/macaque model has been used to identify viral factors that are important for the development of neurological disease, to determine when HIV enters the brain, and to characterize the host immune responses affecting virus entry to the CNS and the development of neurological disease.

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“…This could occur either by direct infection of the EC leading to viral spread into the CNS (Wiley et al, 1986;Rostad et al, 1987;Rao et al, 1993) or by cytokineinduced damage to the blood-brain barrier which may allow the passive entrance of infected cells or viruses (Genis et al, 1992). Vascular alterations have been observed in AIDS-related encephalopathies in human (Smith et al, 1990;Hall et al, 1991 ;Briistle et al, 1992;Burns, 1992;Gray et al, 1993;Power et al, 1993) as well as in cats (Hurtrel et al, 1992).…”

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confidence: 99%

“…Vascular alterations have been observed in AIDS-related encephalopathies in human (Smith et al, 1990;Hall et al, 1991 ;Briistle et al, 1992;Burns, 1992;Gray et al, 1993;Power et al, 1993) as well as in cats (Hurtrel et al, 1992). Several studies revealed the presence of HIV in different cell types, especially in macrophages and microglial cells (Koenig et al, 1986;Parravicini et al, 1989;Briistle et al, 1992;Geleziunas et al, 1992), but also more rarely in astrocytes (Epstein et at., 1985;Mirra & del Rio, 1989), oligodendrocytes (Gyorkey et al, 1987) and EC (Wiley et al, 1986;Pumarola-Sune et al, 1987;Rostad et al, 1987;Ward et al, 1987;Wiley & Nelson, 1988;Smith et al, 1990). Most often, virus-infected microglial cells or macrophages were found in perivascular infiltrates in close contact with EC (Smith et al, 1990).…”

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confidence: 99%

Feline immunodeficiency virus can productively infect cultured endothelial cells from cat brain microvessels

Steffan

Lafon²,

Gendrault³

et al. 1994

Journal of General Virology

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Feline immunodeficiency virus (FIV) provokes a disease in cats characterized by histopathological lesions similar to those observed in AIDS patients. In order to determine whether endothelial cells from brain microvessels are involved in the central nervous system disease to the same extent as macrophages and microglia, cells were isolated from healthy cat brains, cultured and infected in vitro with the FIV Villefranche IFFA 1/88 strain. The isolated cells displayed typical endothelial cell ultrastructural features and were characterized further by yon WiUebrand factor-labelling and the binding of specific lectins such as Ulex europaeus lectin on their membrane. They were also able to take up acetylated low density lipoproteins. Two weeks after infection, significant amounts of FIV p24 antigen were detected by indirect immunofluorescence in syncytia and single cells. Concomitantly, the same antigen could be detected in the culture medium of the infected cells by an ELISA technique. Numerous viral particles as well as different steps in the process of viral budding were observed under transmission electron microscopy. The synthesis of FIV p24 antigens still occurred in cells in which replication was blocked in the G 2 phase with taxol. Our results suggest the possibility of a productive infection of brain microvascular endothelial cells by FIV in vivo, which could lead to important perturbations in the functions of the blood-brain barrier.

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Human Immunodeficiency Virus (HIV) Infection in Brains with AIDS-Related Leukoencephalopathy

Cited by 50 publications

References 20 publications

Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages

Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages

SIV infection of macaques - modeling the progression to AIDS dementia

Feline immunodeficiency virus can productively infect cultured endothelial cells from cat brain microvessels

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