Virus-host interaction in the simian immunodeficiency virus–infected brain

Fox, Howard S.

doi:10.1080/13550280802132824

Cited by 13 publications

(5 citation statements)

References 55 publications

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“…Specifically, Simian Immunodeficiency Virus Encephalitis (SIVE) is an excellent model of HIVE that can be used to assess CNS responses to treatment in Type I impairment. Its ability to address Type II impairment is not as clear-cut [50] , [51] . The same applies to in vitro cellular reconstitution models of HAND, which address neurovirological and neuroimmune changes [52] that are not observed at autopsy in Type II impairment.…”

Section: Discussionmentioning

confidence: 99%

The National NeuroAIDS Tissue Consortium Brain Gene Array: Two Types of HIV-Associated Neurocognitive Impairment

et al. 2012

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BackgroundThe National NeuroAIDS Tissue Consortium (NNTC) performed a brain gene expression array to elucidate pathophysiologies of Human Immunodeficiency Virus type 1 (HIV-1)-associated neurocognitive disorders.MethodsTwenty-four human subjects in four groups were examined A) Uninfected controls; B) HIV-1 infected subjects with no substantial neurocognitive impairment (NCI); C) Infected with substantial NCI without HIV encephalitis (HIVE); D) Infected with substantial NCI and HIVE. RNA from neocortex, white matter, and neostriatum was processed with the Affymetrix® array platform.ResultsWith HIVE the HIV-1 RNA load in brain tissue was three log10 units higher than other groups and over 1,900 gene probes were regulated. Interferon response genes (IFRGs), antigen presentation, complement components and CD163 antigen were strongly upregulated. In frontal neocortex downregulated neuronal pathways strongly dominated in HIVE, including GABA receptors, glutamate signaling, synaptic potentiation, axon guidance, clathrin-mediated endocytosis and 14-3-3 protein. Expression was completely different in neuropsychologically impaired subjects without HIVE. They had low brain HIV-1 loads, weak brain immune responses, lacked neuronally expressed changes in neocortex and exhibited upregulation of endothelial cell type transcripts. HIV-1-infected subjects with normal neuropsychological test results had upregulation of neuronal transcripts involved in synaptic transmission of neostriatal circuits.InterpretationTwo patterns of brain gene expression suggest that more than one pathophysiological process occurs in HIV-1-associated neurocognitive impairment. Expression in HIVE suggests that lowering brain HIV-1 replication might improve NCI, whereas NCI without HIVE may not respond in kind; array results suggest that modulation of transvascular signaling is a potentially promising approach. Striking brain regional differences highlighted the likely importance of circuit level disturbances in HIV/AIDS. In subjects without impairment regulation of genes that drive neostriatal synaptic plasticity reflects adaptation. The array provides an infusion of public resources including brain samples, clinicopathological data and correlative gene expression data for further exploration (http://www.nntc.org/gene-array-project).

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Section: Discussionmentioning

confidence: 99%

The National NeuroAIDS Tissue Consortium Brain Gene Array: Two Types of HIV-Associated Neurocognitive Impairment

et al. 2012

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“…Similarly, reductions in CD4 + or CD8 + T cell numbers were shown to accelerate disease progression and increase viraemia following HIV or SIV infection 80–83 . The presence of CD8 + T cells in the CNS during SIV infection 84,85 suggests local control of viral replication.…”

Section: Persistent and Latent Viral Infectionsmentioning

confidence: 97%

Illuminating viral infections in the nervous system

2011

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Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses.

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“…To examine the affects of HIV-1 genes in vivo , portions of HIV-1 can be inserted into SIV creating hybrid simian-human immunodeficiency virus (SHIV). There are many recent reviews of SIV and SHIV models for HIV-1 neuropathogenesis (Clements et al, 2008; Crews et al, 2008; Fox, 2008; Williams et al, 2008). Most studies focus on the development of terminal disease with SIV encephalitis and much has been learned about its development and pathology, including its in-depth molecular characterization (Roberts et al, 2003)…”

Section: Animal Models For Hiv-1 Neuropathogenesismentioning

confidence: 99%

A Coat of Many Colors: Neuroimmune Crosstalk in Human Immunodeficiency Virus Infection

Kraft-Terry

Buch

Fox

et al. 2009

Neuron

110

125

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The use of antiretroviral therapy (ART) has reduced mortality and increased the quality of life of HIV-1 infected people in more developed countries, where access to treatment is more widespread. However, morbidities continue which include HIV-1 associated neurocognitive disorders (HAND). Subtle cognitive abnormalities and low-level viral replication underlie disease. The balance between robust antiviral adaptive immunity, neuronal homeostatic mechanisms, and neuroprotective factors on one hand and toxicities afforded by dysregulated immune activities on the other govern disease. In the ART era, these lead to chronic low-level infection and often subclinical disease. New insights into the pathobiological processes for neuroimmune-linked disease and ways to modulate such activities for therapeutic gain are discussed. Better understanding the complexities of immune regulation during HAND can improve diagnosis and disease outcomes but is also relevant for the pathogenesis of a broad range of neurodegenerative disorders.

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Virus-host interaction in the simian immunodeficiency virus–infected brain

Cited by 13 publications

References 55 publications

The National NeuroAIDS Tissue Consortium Brain Gene Array: Two Types of HIV-Associated Neurocognitive Impairment

The National NeuroAIDS Tissue Consortium Brain Gene Array: Two Types of HIV-Associated Neurocognitive Impairment

Illuminating viral infections in the nervous system

A Coat of Many Colors: Neuroimmune Crosstalk in Human Immunodeficiency Virus Infection

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