SIV-Induced Immune Activation and Metabolic Alterations in the Dorsal Root Ganglia During Acute Infection

Lisa Mangus, Rachel L. Weinberg, Audrey C. Knight, Suzanne E. Queen, Robert John Adams, Joseph L Mankowski

Research output: Contribution to journalArticle

Abstract

Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls. We found significant upregulation of many genes involved in immune signaling and activation in the DRG. Among genes related to glutamate metabolism, there was significant upregulation of glutamine synthetase (GS), while glutaminase (GLS) was downregulated. Several genes involved in the oxidative stress response also showed significant differential regulation in the DRG of 7d SIV-infected animals, with superoxide dismutase-2 (SOD2) showing the greatest median fold change compared to controls. Novel findings in the DRG were compared to corresponding brain data and further investigated at the protein level by Western blotting and immunohistochemistry. Together with our previous finding of significant epidermal nerve fiber loss at 14 days post-SIV infection, results of this study demonstrate that immune activation and altered cellular metabolism at in the DRG precede and likely contribute to early sensory nerve injury in HIV-SN.

Original languageEnglish (US)
Pages (from-to)78-87
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume78
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Simian Immunodeficiency Virus
Spinal Ganglia
Infection
HIV
Up-Regulation
Glutaminase
Genes
Glutamate-Ammonia Ligase
Peripheral Nervous System
Macaca
Virus Diseases
Nerve Fibers
Nervous System
HIV Infections
Glutamic Acid
Oxidative Stress
Down-Regulation
Western Blotting
Immunohistochemistry
Metabolic Activation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

SIV-Induced Immune Activation and Metabolic Alterations in the Dorsal Root Ganglia During Acute Infection. / Mangus, Lisa; Weinberg, Rachel L.; Knight, Audrey C.; Queen, Suzanne E.; Adams, Robert John; Mankowski, Joseph L.

In: Journal of Neuropathology and Experimental Neurology, Vol. 78, No. 1, 01.01.2019, p. 78-87.

Research output: Contribution to journalArticle

@article{6dc712ce4aef4c728d2fed92a58ac208,
title = "SIV-Induced Immune Activation and Metabolic Alterations in the Dorsal Root Ganglia During Acute Infection",
abstract = "Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls. We found significant upregulation of many genes involved in immune signaling and activation in the DRG. Among genes related to glutamate metabolism, there was significant upregulation of glutamine synthetase (GS), while glutaminase (GLS) was downregulated. Several genes involved in the oxidative stress response also showed significant differential regulation in the DRG of 7d SIV-infected animals, with superoxide dismutase-2 (SOD2) showing the greatest median fold change compared to controls. Novel findings in the DRG were compared to corresponding brain data and further investigated at the protein level by Western blotting and immunohistochemistry. Together with our previous finding of significant epidermal nerve fiber loss at 14 days post-SIV infection, results of this study demonstrate that immune activation and altered cellular metabolism at in the DRG precede and likely contribute to early sensory nerve injury in HIV-SN.",
author = "Lisa Mangus and Weinberg, {Rachel L.} and Knight, {Audrey C.} and Queen, {Suzanne E.} and Adams, {Robert John} and Mankowski, {Joseph L}",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/jnen/nly111",
language = "English (US)",
volume = "78",
pages = "78--87",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - SIV-Induced Immune Activation and Metabolic Alterations in the Dorsal Root Ganglia During Acute Infection

AU - Mangus, Lisa

AU - Weinberg, Rachel L.

AU - Knight, Audrey C.

AU - Queen, Suzanne E.

AU - Adams, Robert John

AU - Mankowski, Joseph L

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls. We found significant upregulation of many genes involved in immune signaling and activation in the DRG. Among genes related to glutamate metabolism, there was significant upregulation of glutamine synthetase (GS), while glutaminase (GLS) was downregulated. Several genes involved in the oxidative stress response also showed significant differential regulation in the DRG of 7d SIV-infected animals, with superoxide dismutase-2 (SOD2) showing the greatest median fold change compared to controls. Novel findings in the DRG were compared to corresponding brain data and further investigated at the protein level by Western blotting and immunohistochemistry. Together with our previous finding of significant epidermal nerve fiber loss at 14 days post-SIV infection, results of this study demonstrate that immune activation and altered cellular metabolism at in the DRG precede and likely contribute to early sensory nerve injury in HIV-SN.

AB - Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls. We found significant upregulation of many genes involved in immune signaling and activation in the DRG. Among genes related to glutamate metabolism, there was significant upregulation of glutamine synthetase (GS), while glutaminase (GLS) was downregulated. Several genes involved in the oxidative stress response also showed significant differential regulation in the DRG of 7d SIV-infected animals, with superoxide dismutase-2 (SOD2) showing the greatest median fold change compared to controls. Novel findings in the DRG were compared to corresponding brain data and further investigated at the protein level by Western blotting and immunohistochemistry. Together with our previous finding of significant epidermal nerve fiber loss at 14 days post-SIV infection, results of this study demonstrate that immune activation and altered cellular metabolism at in the DRG precede and likely contribute to early sensory nerve injury in HIV-SN.

UR - http://www.scopus.com/inward/record.url?scp=85058600073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058600073&partnerID=8YFLogxK

U2 - 10.1093/jnen/nly111

DO - 10.1093/jnen/nly111

M3 - Article

C2 - 30500918

AN - SCOPUS:85058600073

VL - 78

SP - 78

EP - 87

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 1

ER -