Active simian immunodeficiency virus (strain smmPGm) infection in macaque central nervous system correlates with neurologic disease

Marilyn S. Smith, Yafen Niu, Shilpa Buch, Zhuang Li, Istvan Adany, David M. Pinson, Raghava Potula, Francis J. Novembre, Opendra Narayan

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Simian immunodeficiency virus strain smmPGm can induce neuropathology in macaques and is a model for the development of human HIV-related brain injury. For quantitative studies of proviral presence and expression in the central nervous system (CNS), we inoculated 8 macaques intravenously with the virus. Three animals were necropsied 2 to 4 weeks after development of infection, and we obtained lymphoid tissue biopsies from 5 animals before 5 weeks after infection. Peak plasma viral loads averaged 106.76 viral RNA Eq/mL at week 2, whereas cerebrospinal fluid viral loads peaked at 104.4 viral RNA Eq/mL. The proviral DNA loads and viral gag mRNA expression in tissues were quantified by real-time polymerase chain reaction. Two animals developed neurologic disease characterized by meningoencephalitis and meningitis. Proviral DNA levels in CNS tissues of these animals at necropsy revealed 10 5.1 and 103.4 copies/μg of DNA, respectively, whereas viral RNA expression in the CNS reached 100 to 1000 times higher levels than those seen in early necropsies. In sharp contrast, in 2 animals necropsied at later times without CNS disease, virus mRNA expression was not detected in any CNS tissue. Our results are consistent with the hypothesis that active virus expression in the CNS is strongly correlated with neurologic disease and that the event occurs at variable periods after infection.

Original languageEnglish (US)
Pages (from-to)518-530
Number of pages13
JournalJournal of Acquired Immune Deficiency Syndromes
Volume38
Issue number5
DOIs
StatePublished - Apr 15 2005

Fingerprint

Simian Immunodeficiency Virus
Macaca
Nervous System Diseases
Central Nervous System
Viral RNA
Viral Load
Nerve Tissue
Infection
Viruses
Messenger RNA
Meningoencephalitis
Central Nervous System Diseases
DNA
Viral DNA
Human Development
Lymphoid Tissue
Meningitis
Brain Injuries
Cerebrospinal Fluid
Real-Time Polymerase Chain Reaction

Keywords

  • Central nervous system infections
  • Encephalitis
  • HIV
  • Meningitis
  • Neuropathogenesis
  • Simian immunodeficiency virus

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Active simian immunodeficiency virus (strain smmPGm) infection in macaque central nervous system correlates with neurologic disease. / Smith, Marilyn S.; Niu, Yafen; Buch, Shilpa; Li, Zhuang; Adany, Istvan; Pinson, David M.; Potula, Raghava; Novembre, Francis J.; Narayan, Opendra.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 38, No. 5, 15.04.2005, p. 518-530.

Research output: Contribution to journalArticle

Smith, Marilyn S. ; Niu, Yafen ; Buch, Shilpa ; Li, Zhuang ; Adany, Istvan ; Pinson, David M. ; Potula, Raghava ; Novembre, Francis J. ; Narayan, Opendra. / Active simian immunodeficiency virus (strain smmPGm) infection in macaque central nervous system correlates with neurologic disease. In: Journal of Acquired Immune Deficiency Syndromes. 2005 ; Vol. 38, No. 5. pp. 518-530.
@article{82399b2fa27d47a78b1fb28627838904,
title = "Active simian immunodeficiency virus (strain smmPGm) infection in macaque central nervous system correlates with neurologic disease",
abstract = "Simian immunodeficiency virus strain smmPGm can induce neuropathology in macaques and is a model for the development of human HIV-related brain injury. For quantitative studies of proviral presence and expression in the central nervous system (CNS), we inoculated 8 macaques intravenously with the virus. Three animals were necropsied 2 to 4 weeks after development of infection, and we obtained lymphoid tissue biopsies from 5 animals before 5 weeks after infection. Peak plasma viral loads averaged 106.76 viral RNA Eq/mL at week 2, whereas cerebrospinal fluid viral loads peaked at 104.4 viral RNA Eq/mL. The proviral DNA loads and viral gag mRNA expression in tissues were quantified by real-time polymerase chain reaction. Two animals developed neurologic disease characterized by meningoencephalitis and meningitis. Proviral DNA levels in CNS tissues of these animals at necropsy revealed 10 5.1 and 103.4 copies/μg of DNA, respectively, whereas viral RNA expression in the CNS reached 100 to 1000 times higher levels than those seen in early necropsies. In sharp contrast, in 2 animals necropsied at later times without CNS disease, virus mRNA expression was not detected in any CNS tissue. Our results are consistent with the hypothesis that active virus expression in the CNS is strongly correlated with neurologic disease and that the event occurs at variable periods after infection.",
keywords = "Central nervous system infections, Encephalitis, HIV, Meningitis, Neuropathogenesis, Simian immunodeficiency virus",
author = "Smith, {Marilyn S.} and Yafen Niu and Shilpa Buch and Zhuang Li and Istvan Adany and Pinson, {David M.} and Raghava Potula and Novembre, {Francis J.} and Opendra Narayan",
year = "2005",
month = "4",
day = "15",
doi = "10.1097/01.qai.0000156395.65562.99",
language = "English (US)",
volume = "38",
pages = "518--530",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Active simian immunodeficiency virus (strain smmPGm) infection in macaque central nervous system correlates with neurologic disease

AU - Smith, Marilyn S.

AU - Niu, Yafen

AU - Buch, Shilpa

AU - Li, Zhuang

AU - Adany, Istvan

AU - Pinson, David M.

AU - Potula, Raghava

AU - Novembre, Francis J.

AU - Narayan, Opendra

PY - 2005/4/15

Y1 - 2005/4/15

N2 - Simian immunodeficiency virus strain smmPGm can induce neuropathology in macaques and is a model for the development of human HIV-related brain injury. For quantitative studies of proviral presence and expression in the central nervous system (CNS), we inoculated 8 macaques intravenously with the virus. Three animals were necropsied 2 to 4 weeks after development of infection, and we obtained lymphoid tissue biopsies from 5 animals before 5 weeks after infection. Peak plasma viral loads averaged 106.76 viral RNA Eq/mL at week 2, whereas cerebrospinal fluid viral loads peaked at 104.4 viral RNA Eq/mL. The proviral DNA loads and viral gag mRNA expression in tissues were quantified by real-time polymerase chain reaction. Two animals developed neurologic disease characterized by meningoencephalitis and meningitis. Proviral DNA levels in CNS tissues of these animals at necropsy revealed 10 5.1 and 103.4 copies/μg of DNA, respectively, whereas viral RNA expression in the CNS reached 100 to 1000 times higher levels than those seen in early necropsies. In sharp contrast, in 2 animals necropsied at later times without CNS disease, virus mRNA expression was not detected in any CNS tissue. Our results are consistent with the hypothesis that active virus expression in the CNS is strongly correlated with neurologic disease and that the event occurs at variable periods after infection.

AB - Simian immunodeficiency virus strain smmPGm can induce neuropathology in macaques and is a model for the development of human HIV-related brain injury. For quantitative studies of proviral presence and expression in the central nervous system (CNS), we inoculated 8 macaques intravenously with the virus. Three animals were necropsied 2 to 4 weeks after development of infection, and we obtained lymphoid tissue biopsies from 5 animals before 5 weeks after infection. Peak plasma viral loads averaged 106.76 viral RNA Eq/mL at week 2, whereas cerebrospinal fluid viral loads peaked at 104.4 viral RNA Eq/mL. The proviral DNA loads and viral gag mRNA expression in tissues were quantified by real-time polymerase chain reaction. Two animals developed neurologic disease characterized by meningoencephalitis and meningitis. Proviral DNA levels in CNS tissues of these animals at necropsy revealed 10 5.1 and 103.4 copies/μg of DNA, respectively, whereas viral RNA expression in the CNS reached 100 to 1000 times higher levels than those seen in early necropsies. In sharp contrast, in 2 animals necropsied at later times without CNS disease, virus mRNA expression was not detected in any CNS tissue. Our results are consistent with the hypothesis that active virus expression in the CNS is strongly correlated with neurologic disease and that the event occurs at variable periods after infection.

KW - Central nervous system infections

KW - Encephalitis

KW - HIV

KW - Meningitis

KW - Neuropathogenesis

KW - Simian immunodeficiency virus

UR - http://www.scopus.com/inward/record.url?scp=17144366630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17144366630&partnerID=8YFLogxK

U2 - 10.1097/01.qai.0000156395.65562.99

DO - 10.1097/01.qai.0000156395.65562.99

M3 - Article

C2 - 15793361

AN - SCOPUS:17144366630

VL - 38

SP - 518

EP - 530

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 5

ER -