Compartmentalization of HIV-1 in the central nervous system: Role of the choroid plexus

Evan J. Burkala, Jun He, John T West, Charles Wood, Carol K. Petito

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Objectives: To determine the genetic and phenotypic composition of HIV-1 found in the choroid plexus (CPx) and its relationship to virus in the brain and peripheral lymphoid tissue. Design: Phenotypic and molecular comparisons of HIV-1 found in autopsy brain, CPx, and spleen tissues. Methods: HIV-1 was co-cultured from matched postmortem brain (basal ganglia), CPx, and spleen tissues of AIDS patients with and without HIV-associated encephalitis and dementia. Viral phenotypes were determined by infection of monocyte-derived macrophages, MT-2 or co-receptor-specific cell lines. Viral env and pol sequences were determined from genomic DNA isolated directly from tissues or co-cultures, and phylogenetic comparisons were performed. Results: CCR5-utilization was the most prevalent viral tropism found in all tissues, although spleen isolates also displayed CXCR4 usage. Viruses isolated from CPx consisted of both peripheral and brain-like virus, but were more related phenotypically and genetically to those found in the brain. Mutations found in the pol gene that could confer drug resistance to brain and CPx isolates were similar to those found in the periphery. Conclusion: The CPx contained replication-competent virus that was most similar, although distinct from that found in the brain. It also contained some viruses with high similarity to those of peripheral origin. Compartmentalization of viral env and pol sequences indicated that differential selective pressures exist in each tissue examined. These studies suggest that the CPx may provide an environment that promotes the evolution of drug-resistant strains with central nervous system tropism, although it is unlikely to be a reservoir for archival HIV-1 variants.

Original languageEnglish (US)
Pages (from-to)675-684
Number of pages10
JournalAIDS
Volume19
Issue number7
DOIs
StatePublished - Apr 29 2005

Fingerprint

Choroid Plexus
HIV-1
Central Nervous System
Brain
Viruses
Spleen
Viral Tropism
AIDS Dementia Complex
pol Genes
Tropism
Lymphoid Tissue
Encephalitis
Virus Replication
Coculture Techniques
Basal Ganglia
Drug Resistance
Autopsy
Acquired Immunodeficiency Syndrome
Macrophages
Phenotype

Keywords

  • Brain
  • Choroid plexus
  • Compartmentalization
  • Drug resistance
  • HIV-1
  • env
  • pol

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Compartmentalization of HIV-1 in the central nervous system : Role of the choroid plexus. / Burkala, Evan J.; He, Jun; West, John T; Wood, Charles; Petito, Carol K.

In: AIDS, Vol. 19, No. 7, 29.04.2005, p. 675-684.

Research output: Contribution to journalArticle

Burkala, Evan J. ; He, Jun ; West, John T ; Wood, Charles ; Petito, Carol K. / Compartmentalization of HIV-1 in the central nervous system : Role of the choroid plexus. In: AIDS. 2005 ; Vol. 19, No. 7. pp. 675-684.
@article{2faeebd516644c8eb7f52010fc2bf27f,
title = "Compartmentalization of HIV-1 in the central nervous system: Role of the choroid plexus",
abstract = "Objectives: To determine the genetic and phenotypic composition of HIV-1 found in the choroid plexus (CPx) and its relationship to virus in the brain and peripheral lymphoid tissue. Design: Phenotypic and molecular comparisons of HIV-1 found in autopsy brain, CPx, and spleen tissues. Methods: HIV-1 was co-cultured from matched postmortem brain (basal ganglia), CPx, and spleen tissues of AIDS patients with and without HIV-associated encephalitis and dementia. Viral phenotypes were determined by infection of monocyte-derived macrophages, MT-2 or co-receptor-specific cell lines. Viral env and pol sequences were determined from genomic DNA isolated directly from tissues or co-cultures, and phylogenetic comparisons were performed. Results: CCR5-utilization was the most prevalent viral tropism found in all tissues, although spleen isolates also displayed CXCR4 usage. Viruses isolated from CPx consisted of both peripheral and brain-like virus, but were more related phenotypically and genetically to those found in the brain. Mutations found in the pol gene that could confer drug resistance to brain and CPx isolates were similar to those found in the periphery. Conclusion: The CPx contained replication-competent virus that was most similar, although distinct from that found in the brain. It also contained some viruses with high similarity to those of peripheral origin. Compartmentalization of viral env and pol sequences indicated that differential selective pressures exist in each tissue examined. These studies suggest that the CPx may provide an environment that promotes the evolution of drug-resistant strains with central nervous system tropism, although it is unlikely to be a reservoir for archival HIV-1 variants.",
keywords = "Brain, Choroid plexus, Compartmentalization, Drug resistance, HIV-1, env, pol",
author = "Burkala, {Evan J.} and Jun He and West, {John T} and Charles Wood and Petito, {Carol K.}",
year = "2005",
month = "4",
day = "29",
doi = "10.1097/01.aids.0000166090.31693.aa",
language = "English (US)",
volume = "19",
pages = "675--684",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - Compartmentalization of HIV-1 in the central nervous system

T2 - Role of the choroid plexus

AU - Burkala, Evan J.

AU - He, Jun

AU - West, John T

AU - Wood, Charles

AU - Petito, Carol K.

PY - 2005/4/29

Y1 - 2005/4/29

N2 - Objectives: To determine the genetic and phenotypic composition of HIV-1 found in the choroid plexus (CPx) and its relationship to virus in the brain and peripheral lymphoid tissue. Design: Phenotypic and molecular comparisons of HIV-1 found in autopsy brain, CPx, and spleen tissues. Methods: HIV-1 was co-cultured from matched postmortem brain (basal ganglia), CPx, and spleen tissues of AIDS patients with and without HIV-associated encephalitis and dementia. Viral phenotypes were determined by infection of monocyte-derived macrophages, MT-2 or co-receptor-specific cell lines. Viral env and pol sequences were determined from genomic DNA isolated directly from tissues or co-cultures, and phylogenetic comparisons were performed. Results: CCR5-utilization was the most prevalent viral tropism found in all tissues, although spleen isolates also displayed CXCR4 usage. Viruses isolated from CPx consisted of both peripheral and brain-like virus, but were more related phenotypically and genetically to those found in the brain. Mutations found in the pol gene that could confer drug resistance to brain and CPx isolates were similar to those found in the periphery. Conclusion: The CPx contained replication-competent virus that was most similar, although distinct from that found in the brain. It also contained some viruses with high similarity to those of peripheral origin. Compartmentalization of viral env and pol sequences indicated that differential selective pressures exist in each tissue examined. These studies suggest that the CPx may provide an environment that promotes the evolution of drug-resistant strains with central nervous system tropism, although it is unlikely to be a reservoir for archival HIV-1 variants.

AB - Objectives: To determine the genetic and phenotypic composition of HIV-1 found in the choroid plexus (CPx) and its relationship to virus in the brain and peripheral lymphoid tissue. Design: Phenotypic and molecular comparisons of HIV-1 found in autopsy brain, CPx, and spleen tissues. Methods: HIV-1 was co-cultured from matched postmortem brain (basal ganglia), CPx, and spleen tissues of AIDS patients with and without HIV-associated encephalitis and dementia. Viral phenotypes were determined by infection of monocyte-derived macrophages, MT-2 or co-receptor-specific cell lines. Viral env and pol sequences were determined from genomic DNA isolated directly from tissues or co-cultures, and phylogenetic comparisons were performed. Results: CCR5-utilization was the most prevalent viral tropism found in all tissues, although spleen isolates also displayed CXCR4 usage. Viruses isolated from CPx consisted of both peripheral and brain-like virus, but were more related phenotypically and genetically to those found in the brain. Mutations found in the pol gene that could confer drug resistance to brain and CPx isolates were similar to those found in the periphery. Conclusion: The CPx contained replication-competent virus that was most similar, although distinct from that found in the brain. It also contained some viruses with high similarity to those of peripheral origin. Compartmentalization of viral env and pol sequences indicated that differential selective pressures exist in each tissue examined. These studies suggest that the CPx may provide an environment that promotes the evolution of drug-resistant strains with central nervous system tropism, although it is unlikely to be a reservoir for archival HIV-1 variants.

KW - Brain

KW - Choroid plexus

KW - Compartmentalization

KW - Drug resistance

KW - HIV-1

KW - env

KW - pol

UR - http://www.scopus.com/inward/record.url?scp=17844371103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17844371103&partnerID=8YFLogxK

U2 - 10.1097/01.aids.0000166090.31693.aa

DO - 10.1097/01.aids.0000166090.31693.aa

M3 - Article

C2 - 15821393

AN - SCOPUS:17844371103

VL - 19

SP - 675

EP - 684

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 7

ER -