In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques

Sanjeev Gumber, Praveen Kumar Amancha, Po Jen Yen, Francois Villinger, Dana Gabuzda, Siddappa Nagadenahalli Byrareddy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.

Original languageEnglish (US)
Pages (from-to)411-419
Number of pages9
JournalJournal of neurovirology
Volume24
Issue number4
DOIs
StatePublished - Aug 1 2018

Fingerprint

Simian Immunodeficiency Virus
Macaca mulatta
Clone Cells
Macrophages
Macaca
HIV Infections
Brain
Myeloid Cells
Encephalitis
Giant Cells
Viral Load
Disease Progression
Colon
Central Nervous System
Lymph Nodes
T-Lymphocytes
Lung
Liver
Infection

Keywords

  • Central nerveous system
  • Macrophage-tropic
  • Macrophages
  • Myeloid cells
  • Rhesus macaques
  • SIV

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Cite this

In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques. / Gumber, Sanjeev; Amancha, Praveen Kumar; Yen, Po Jen; Villinger, Francois; Gabuzda, Dana; Byrareddy, Siddappa Nagadenahalli.

In: Journal of neurovirology, Vol. 24, No. 4, 01.08.2018, p. 411-419.

Research output: Contribution to journalArticle

Gumber, Sanjeev ; Amancha, Praveen Kumar ; Yen, Po Jen ; Villinger, Francois ; Gabuzda, Dana ; Byrareddy, Siddappa Nagadenahalli. / In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques. In: Journal of neurovirology. 2018 ; Vol. 24, No. 4. pp. 411-419.
@article{9e464c060da149e282a492a259b2c7d0,
title = "In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques",
abstract = "Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.",
keywords = "Central nerveous system, Macrophage-tropic, Macrophages, Myeloid cells, Rhesus macaques, SIV",
author = "Sanjeev Gumber and Amancha, {Praveen Kumar} and Yen, {Po Jen} and Francois Villinger and Dana Gabuzda and Byrareddy, {Siddappa Nagadenahalli}",
year = "2018",
month = "8",
day = "1",
doi = "10.1007/s13365-018-0628-2",
language = "English (US)",
volume = "24",
pages = "411--419",
journal = "Journal of NeuroVirology",
issn = "1355-0284",
publisher = "Springer New York",
number = "4",

}

TY - JOUR

T1 - In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques

AU - Gumber, Sanjeev

AU - Amancha, Praveen Kumar

AU - Yen, Po Jen

AU - Villinger, Francois

AU - Gabuzda, Dana

AU - Byrareddy, Siddappa Nagadenahalli

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.

AB - Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.

KW - Central nerveous system

KW - Macrophage-tropic

KW - Macrophages

KW - Myeloid cells

KW - Rhesus macaques

KW - SIV

UR - http://www.scopus.com/inward/record.url?scp=85045050741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045050741&partnerID=8YFLogxK

U2 - 10.1007/s13365-018-0628-2

DO - 10.1007/s13365-018-0628-2

M3 - Article

C2 - 29594984

AN - SCOPUS:85045050741

VL - 24

SP - 411

EP - 419

JO - Journal of NeuroVirology

JF - Journal of NeuroVirology

SN - 1355-0284

IS - 4

ER -