HIV-1 clade B and C isolates exhibit differential replication

Relevance to macrophage-mediated neurotoxicity

Agnes A. Constantino, Yunlong Huang, Hong Zhang, Charles Wood, Jialin C Zheng

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

HIV-associated neurocognitive disorders (HAND) continue to be a consequence of HIV-1 infection among clade B-infected individuals. In contrast, the incidence of severe neurological impairment is lower among clade C-infected patients in regions of Sub-Saharan Africa and India. Biological aspects such as replication, cytopathicity, inflammatory response, and neurotoxicity unique to each clade influence neuropathogenicity and ultimately affect the clinical outcome of the disease. We hypothesize that productive infection by clade C isolates leads to macrophage- mediated neurotoxicity, although to a lesser extent than clade B isolates. Using a panel of primary isolates of clades B and C we demonstrated that clade B has higher replication efficiency in monocyte-derived macrophages (MDM) through reverse transcriptase activity assay and HIV-1 p24 antigen ELISA. To test the neurotoxicity of clades B and C, we used an in vitro neurotoxicity model. Conditioned medium from clade B-infected MDM was neurotoxic to rat and human neuron cultures. In contrast, clade C isolates mediated neurotoxicity when a higher initial viral titer was used for MDM infection. Furthermore, neurotoxicity mediated by isolates of both clades correlated with virus replication in MDM. Together, these results suggest that in comparison to clade B, primary isolates of clade C have slower replication kinetics in primary MDM, leading to lower levels of macrophage-mediated neurotoxicity. Elucidating the differences in replication and macrophage- mediated neurotoxicity between isolates of HIV-1 clades B and C will provide important insights needed to clarify the disparity seen in HAND incidence.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalNeurotoxicity Research
Volume20
Issue number3
DOIs
StatePublished - Oct 1 2011

Fingerprint

Macrophages
HIV-1
HIV Core Protein p24
HIV
Africa South of the Sahara
RNA-Directed DNA Polymerase
Incidence
Conditioned Culture Medium
Virus Replication
Infection
Viruses
Cell culture
Neurons
HIV Infections
Rats
India
Assays
Enzyme-Linked Immunosorbent Assay
Antigens
Kinetics

Keywords

  • HIV-1 clade B
  • HIV-1 clade C
  • HIV-associated neurocognitive disorders
  • Macrophages
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

HIV-1 clade B and C isolates exhibit differential replication : Relevance to macrophage-mediated neurotoxicity. / Constantino, Agnes A.; Huang, Yunlong; Zhang, Hong; Wood, Charles; Zheng, Jialin C.

In: Neurotoxicity Research, Vol. 20, No. 3, 01.10.2011, p. 277-288.

Research output: Contribution to journalArticle

@article{2cc0b77e9cb54b45901555ef3d731c2e,
title = "HIV-1 clade B and C isolates exhibit differential replication: Relevance to macrophage-mediated neurotoxicity",
abstract = "HIV-associated neurocognitive disorders (HAND) continue to be a consequence of HIV-1 infection among clade B-infected individuals. In contrast, the incidence of severe neurological impairment is lower among clade C-infected patients in regions of Sub-Saharan Africa and India. Biological aspects such as replication, cytopathicity, inflammatory response, and neurotoxicity unique to each clade influence neuropathogenicity and ultimately affect the clinical outcome of the disease. We hypothesize that productive infection by clade C isolates leads to macrophage- mediated neurotoxicity, although to a lesser extent than clade B isolates. Using a panel of primary isolates of clades B and C we demonstrated that clade B has higher replication efficiency in monocyte-derived macrophages (MDM) through reverse transcriptase activity assay and HIV-1 p24 antigen ELISA. To test the neurotoxicity of clades B and C, we used an in vitro neurotoxicity model. Conditioned medium from clade B-infected MDM was neurotoxic to rat and human neuron cultures. In contrast, clade C isolates mediated neurotoxicity when a higher initial viral titer was used for MDM infection. Furthermore, neurotoxicity mediated by isolates of both clades correlated with virus replication in MDM. Together, these results suggest that in comparison to clade B, primary isolates of clade C have slower replication kinetics in primary MDM, leading to lower levels of macrophage-mediated neurotoxicity. Elucidating the differences in replication and macrophage- mediated neurotoxicity between isolates of HIV-1 clades B and C will provide important insights needed to clarify the disparity seen in HAND incidence.",
keywords = "HIV-1 clade B, HIV-1 clade C, HIV-associated neurocognitive disorders, Macrophages, Neurotoxicity",
author = "Constantino, {Agnes A.} and Yunlong Huang and Hong Zhang and Charles Wood and Zheng, {Jialin C}",
year = "2011",
month = "10",
day = "1",
doi = "10.1007/s12640-011-9241-3",
language = "English (US)",
volume = "20",
pages = "277--288",
journal = "Neurotoxicity Research",
issn = "1029-8428",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - HIV-1 clade B and C isolates exhibit differential replication

T2 - Relevance to macrophage-mediated neurotoxicity

AU - Constantino, Agnes A.

AU - Huang, Yunlong

AU - Zhang, Hong

AU - Wood, Charles

AU - Zheng, Jialin C

PY - 2011/10/1

Y1 - 2011/10/1

N2 - HIV-associated neurocognitive disorders (HAND) continue to be a consequence of HIV-1 infection among clade B-infected individuals. In contrast, the incidence of severe neurological impairment is lower among clade C-infected patients in regions of Sub-Saharan Africa and India. Biological aspects such as replication, cytopathicity, inflammatory response, and neurotoxicity unique to each clade influence neuropathogenicity and ultimately affect the clinical outcome of the disease. We hypothesize that productive infection by clade C isolates leads to macrophage- mediated neurotoxicity, although to a lesser extent than clade B isolates. Using a panel of primary isolates of clades B and C we demonstrated that clade B has higher replication efficiency in monocyte-derived macrophages (MDM) through reverse transcriptase activity assay and HIV-1 p24 antigen ELISA. To test the neurotoxicity of clades B and C, we used an in vitro neurotoxicity model. Conditioned medium from clade B-infected MDM was neurotoxic to rat and human neuron cultures. In contrast, clade C isolates mediated neurotoxicity when a higher initial viral titer was used for MDM infection. Furthermore, neurotoxicity mediated by isolates of both clades correlated with virus replication in MDM. Together, these results suggest that in comparison to clade B, primary isolates of clade C have slower replication kinetics in primary MDM, leading to lower levels of macrophage-mediated neurotoxicity. Elucidating the differences in replication and macrophage- mediated neurotoxicity between isolates of HIV-1 clades B and C will provide important insights needed to clarify the disparity seen in HAND incidence.

AB - HIV-associated neurocognitive disorders (HAND) continue to be a consequence of HIV-1 infection among clade B-infected individuals. In contrast, the incidence of severe neurological impairment is lower among clade C-infected patients in regions of Sub-Saharan Africa and India. Biological aspects such as replication, cytopathicity, inflammatory response, and neurotoxicity unique to each clade influence neuropathogenicity and ultimately affect the clinical outcome of the disease. We hypothesize that productive infection by clade C isolates leads to macrophage- mediated neurotoxicity, although to a lesser extent than clade B isolates. Using a panel of primary isolates of clades B and C we demonstrated that clade B has higher replication efficiency in monocyte-derived macrophages (MDM) through reverse transcriptase activity assay and HIV-1 p24 antigen ELISA. To test the neurotoxicity of clades B and C, we used an in vitro neurotoxicity model. Conditioned medium from clade B-infected MDM was neurotoxic to rat and human neuron cultures. In contrast, clade C isolates mediated neurotoxicity when a higher initial viral titer was used for MDM infection. Furthermore, neurotoxicity mediated by isolates of both clades correlated with virus replication in MDM. Together, these results suggest that in comparison to clade B, primary isolates of clade C have slower replication kinetics in primary MDM, leading to lower levels of macrophage-mediated neurotoxicity. Elucidating the differences in replication and macrophage- mediated neurotoxicity between isolates of HIV-1 clades B and C will provide important insights needed to clarify the disparity seen in HAND incidence.

KW - HIV-1 clade B

KW - HIV-1 clade C

KW - HIV-associated neurocognitive disorders

KW - Macrophages

KW - Neurotoxicity

UR - http://www.scopus.com/inward/record.url?scp=84855682051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855682051&partnerID=8YFLogxK

U2 - 10.1007/s12640-011-9241-3

DO - 10.1007/s12640-011-9241-3

M3 - Article

VL - 20

SP - 277

EP - 288

JO - Neurotoxicity Research

JF - Neurotoxicity Research

SN - 1029-8428

IS - 3

ER -