Host Response and Dysfunction in the CNS during Chronic Simian Immunodeficiency Virus Infection

Roberts, Eleanor; Huitrón‐Reséndiz, Salvador; Taffe, Michael A.; Marcondes, Maria Cecília Garibaldi; Flynn, Claudia T.; Lanigan, Caroline; Hammond, Jennifer; Head, Steven R.; Henriksen, Steven J.; Fox, Howard S.

doi:10.1523/jneurosci.4504-05.2006

Cited by 34 publications

(35 citation statements)

References 65 publications

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“…In the brain, when compared with uninfected monkeys, there was a significant (5.6-fold, p ϭ 0.002, two-tailed t test) increase in the number of CD8 ϩ T cells, consistent with our previous findings (3,6,7).…”

Section: Tissue Ctl Specificitysupporting

confidence: 91%

“…CD8 ϩ T cells isolated at early time points have altered phenotypes relative to those from uninfected brains, in that they now express CTL effector molecules (6). The brain viral load then decreases by 10-to a 1000-fold, but the CD8 ϩ T cells increase in number in the brain and persist in this phase of infection (6,7). The relationship between the CNS CTL response and that in the periphery is unknown.…”

mentioning

confidence: 99%

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Enrichment and Persistence of Virus-Specific CTL in the Brain of Simian Immunodeficiency Virus-Infected Monkeys Is Associated with a Unique Cytokine Environment

Marcondes

Burdo

Sopper

et al. 2007

The Journal of Immunology

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The host reaction to infection of the brain contributes to a number of CNS pathologies including neuro-AIDS. In this study, we have identified the accumulation of SIV-specific CTL in the brains of SIV-infected animals who have neurophysiological abnormalities but are otherwise asymptomatic. SIV-specific CTL enter the brain early after viral infection and are maintained in the brain even when those reactive with an immunodominant epitope in Tat are lost from the rest of the body. The specialized CNS environment contributes to this unique outcome. Following SIV infection, brain levels of IL-15 were significantly elevated whereas IL-2 was absent, creating an environment that favors CTL persistence. Furthermore, in response to IL-15, brain-derived CD8+ T cells could expand in greater numbers than those from spleen. The accumulation, persistence, and maintenance of CTL in the brain are closely linked to the increased levels of IL-15 in the absence of IL-2 in the CNS following SIV infection.

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Section: Tissue Ctl Specificitysupporting

confidence: 91%

mentioning

confidence: 99%

Enrichment and Persistence of Virus-Specific CTL in the Brain of Simian Immunodeficiency Virus-Infected Monkeys Is Associated with a Unique Cytokine Environment

Marcondes

Burdo

Sopper

et al. 2007

The Journal of Immunology

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“…In regard to chronic infection, 2 years after SIV infection of rhesus macaques, nervous system dysfunction is readily demonstrated. In these animals, infiltrating CD8 ϩ T cells were found in the brain (64). For feline immunodeficiency virus infection of cats, brain disease is characterized by infiltrates of CD79 ϩ and CD3 ϩ B and T cells (mixture of CD4 ϩ and CD8 ϩ cells).…”

Section: Discussionmentioning

confidence: 97%

Copolymer-1 Induces Adaptive Immune Anti-inflammatory Glial and Neuroprotective Responses in a Murine Model of HIV-1 Encephalitis

Gorantla

Liu²,

Sneller

et al. 2007

The Journal of Immunology

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Copolymer-1 (COP-1) elicits neuroprotective activities in a wide range of neurodegenerative disorders. This occurs, in part, by adaptive immune-mediated suppression of microglial inflammatory responses. Because HIV infection and immune activation of perivascular macrophages and microglia drive a metabolic encephalopathy, we reasoned that COP-1 could be developed as an adjunctive therapy for disease. To test this, we developed a novel animal model system that reflects HIV-1 encephalitis in rodents with both innate and adaptive arms of the immune system. Bone marrow-derived macrophages were infected with HIV-1/vesicular stomatitis-pseudotyped virus and stereotactically injected into the basal ganglia of syngeneic mice. HIV-1 pseudotyped with vesicular stomatitis virus envelope-infected bone marrow-derived macrophages induced significant neuroinflammation, including astrogliosis and microglial activation with subsequent neuronal damage. Importantly, COP-1 immunization reduced astro- and microgliosis while diminishing neurodegeneration. Hippocampal neurogenesis was, in part, restored. This paralleled reductions in proinflammatory cytokines, including TNF-α and IL-1β, and inducible NO synthase, and increases in brain-derived neurotrophic factor. Ingress of Foxp3- and IL-4-expressing lymphocytes into brains of COP-1-immunized animals was observed. We conclude that COP-1 may warrant therapeutic consideration for HIV-1-associated cognitive impairments.

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“…The data reported here came from three retinal preparations (1-3), each from a different macaque monkey. The macaques for prep-arations 1 and 3 were experimentally infected with the simian immunodeficiency virus (Roberts et al, 2006); the macaque for preparation 2 was uninfected. No differences were observed in the retinal response properties for the preparations from the infected macaques compared with the uninfected macaque.…”

Section: Methodsmentioning

confidence: 99%

Identification and Characterization of a Y-Like Primate Retinal Ganglion Cell Type

Petrusca

Grivich²,

Sher³

et al. 2007

J. Neurosci.

154

227

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The primate retina communicates visual information to the brain via a set of parallel pathways that originate from at least 22 anatomically distinct types of retinal ganglion cells. Knowledge of the physiological properties of these ganglion cell types is of critical importance for understanding the functioning of the primate visual system. Nonetheless, the physiological properties of only a handful of retinal ganglion cell types have been studied in detail. Here we show, using a newly developed multielectrode array system for the large-scale recording of neural activity, the existence of a physiologically distinct population of ganglion cells in the primate retina with distinctive visual response properties. These cells, which we will refer to as upsilon cells, are characterized by large receptive fields, rapid and transient responses to light, and significant nonlinearities in their spatial summation. Based on the measured properties of these cells, we speculate that they correspond to the smooth/large radiate cells recently identified morphologically in the primate retina and may therefore provide visual input to both the lateral geniculate nucleus and the superior colliculus. We further speculate that the upsilon cells may be the primate retina's counterparts of the Y-cells observed in the cat and other mammalian species.

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Host Response and Dysfunction in the CNS during Chronic Simian Immunodeficiency Virus Infection

Cited by 34 publications

References 65 publications

Enrichment and Persistence of Virus-Specific CTL in the Brain of Simian Immunodeficiency Virus-Infected Monkeys Is Associated with a Unique Cytokine Environment

Enrichment and Persistence of Virus-Specific CTL in the Brain of Simian Immunodeficiency Virus-Infected Monkeys Is Associated with a Unique Cytokine Environment

Copolymer-1 Induces Adaptive Immune Anti-inflammatory Glial and Neuroprotective Responses in a Murine Model of HIV-1 Encephalitis

Identification and Characterization of a Y-Like Primate Retinal Ganglion Cell Type

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