The central nervous system as a reservoir for simian immunodeficiency virus (SIV): Steady-state levels of SIV DNA in brain from acute through asymptomatic infection

Janice E Clements, Tahar Babas, Joseph L Mankowski, K. Suryanarayana, Michael Piatak, Patrick Tarwater, Jeffrey D. Lifson, Mary Christine Zink

Research output: Contribution to journalArticle

Abstract

Latent reservoirs of human immunodeficiency virus (HIV) present significant challenges for eradicating HIV from infected persons, particularly reservoirs in the brain established during acute infection. A simian immunodeficiency virus (SIV)/macaque model of HIV dementia was used to show that viral DNA levels in the brain remained at constant levels from acute through asymptomatic infection, despite significant down-regulation of viral RNA in the brain after the acute phase of infection. Viral replication in the brain coincided with activation of macrophages and microglia in the central nervous system; down-regulation of viral replication coincided with increased infiltration of cytotoxic lymphocytes and reduced activation of macrophages and microglia in the brain. Comparison of viral genotypes in the central nervous system and peripheral blood mononuclear cells suggests that recrudescence of viral replication in brain occurs by reactivation of latent viral DNA. Latent virus in the brain must be considered in therapeutic strategies to eliminate HIV from infected persons.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalJournal of Infectious Diseases
Volume186
Issue number7
DOIs
StatePublished - Oct 1 2002

Fingerprint

Simian Immunodeficiency Virus
Asymptomatic Infections
Central Nervous System
DNA
Brain
HIV
Viral DNA
Microglia
Down-Regulation
Macrophage Activation
Viral RNA
Macaca
Lymphocyte Activation
Infection
Dementia
Blood Cells
Macrophages
Genotype
Viruses
Recurrence

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

@article{3ba67ae8616a44b8b0933f4af37aa9ae,
title = "The central nervous system as a reservoir for simian immunodeficiency virus (SIV): Steady-state levels of SIV DNA in brain from acute through asymptomatic infection",
abstract = "Latent reservoirs of human immunodeficiency virus (HIV) present significant challenges for eradicating HIV from infected persons, particularly reservoirs in the brain established during acute infection. A simian immunodeficiency virus (SIV)/macaque model of HIV dementia was used to show that viral DNA levels in the brain remained at constant levels from acute through asymptomatic infection, despite significant down-regulation of viral RNA in the brain after the acute phase of infection. Viral replication in the brain coincided with activation of macrophages and microglia in the central nervous system; down-regulation of viral replication coincided with increased infiltration of cytotoxic lymphocytes and reduced activation of macrophages and microglia in the brain. Comparison of viral genotypes in the central nervous system and peripheral blood mononuclear cells suggests that recrudescence of viral replication in brain occurs by reactivation of latent viral DNA. Latent virus in the brain must be considered in therapeutic strategies to eliminate HIV from infected persons.",
author = "Clements, {Janice E} and Tahar Babas and Mankowski, {Joseph L} and K. Suryanarayana and Michael Piatak and Patrick Tarwater and Lifson, {Jeffrey D.} and Zink, {Mary Christine}",
year = "2002",
month = "10",
day = "1",
doi = "10.1086/343768",
language = "English (US)",
volume = "186",
pages = "905--913",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - The central nervous system as a reservoir for simian immunodeficiency virus (SIV)

T2 - Steady-state levels of SIV DNA in brain from acute through asymptomatic infection

AU - Clements, Janice E

AU - Babas, Tahar

AU - Mankowski, Joseph L

AU - Suryanarayana, K.

AU - Piatak, Michael

AU - Tarwater, Patrick

AU - Lifson, Jeffrey D.

AU - Zink, Mary Christine

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Latent reservoirs of human immunodeficiency virus (HIV) present significant challenges for eradicating HIV from infected persons, particularly reservoirs in the brain established during acute infection. A simian immunodeficiency virus (SIV)/macaque model of HIV dementia was used to show that viral DNA levels in the brain remained at constant levels from acute through asymptomatic infection, despite significant down-regulation of viral RNA in the brain after the acute phase of infection. Viral replication in the brain coincided with activation of macrophages and microglia in the central nervous system; down-regulation of viral replication coincided with increased infiltration of cytotoxic lymphocytes and reduced activation of macrophages and microglia in the brain. Comparison of viral genotypes in the central nervous system and peripheral blood mononuclear cells suggests that recrudescence of viral replication in brain occurs by reactivation of latent viral DNA. Latent virus in the brain must be considered in therapeutic strategies to eliminate HIV from infected persons.

AB - Latent reservoirs of human immunodeficiency virus (HIV) present significant challenges for eradicating HIV from infected persons, particularly reservoirs in the brain established during acute infection. A simian immunodeficiency virus (SIV)/macaque model of HIV dementia was used to show that viral DNA levels in the brain remained at constant levels from acute through asymptomatic infection, despite significant down-regulation of viral RNA in the brain after the acute phase of infection. Viral replication in the brain coincided with activation of macrophages and microglia in the central nervous system; down-regulation of viral replication coincided with increased infiltration of cytotoxic lymphocytes and reduced activation of macrophages and microglia in the brain. Comparison of viral genotypes in the central nervous system and peripheral blood mononuclear cells suggests that recrudescence of viral replication in brain occurs by reactivation of latent viral DNA. Latent virus in the brain must be considered in therapeutic strategies to eliminate HIV from infected persons.

UR - http://www.scopus.com/inward/record.url?scp=0036786355&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036786355&partnerID=8YFLogxK

U2 - 10.1086/343768

DO - 10.1086/343768

M3 - Article

C2 - 12232830

AN - SCOPUS:0036786355

VL - 186

SP - 905

EP - 913

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 7

ER -