Development and characterization of positively selected brain-adapted SIV

Peter J. Gaskill, Debbie D. Watry, Tricia H. Burdo, Howard S Fox

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

HIV is found in the brains of most infected individuals but only 30% develop neurological disease. Both viral and host factors are thought to contribute to the motor and cognitive disorders resulting from HIV infection. Here, using the SIV/rhesus monkey system, we characterize the salient characteristics of the virus from the brain of animals with neuropathological disorders. Nine unique molecular clones of SIV were derived from virus released by microglia cultured from the brains of two macaques with SIV encephalitis. Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR. As this genotype was found in the brains of two separate animals, and it encoded a set of distinct amino acid changes from the infecting virus, it demonstrates the convergent evolution of the virus to a unique brain-adapted genotype. This genotype was distinct from other macrophage-tropic and neurovirulent strains of SIV. Functional characterization of virus derived from representative clones showed a robust in vitro infection of 174xCEM cells, primary macrophages and primary microglia. The infectious phenotype of this virus is distinct from that shown by other strains of SIV, potentially reflecting the method by which the virus successfully infiltrates and infects the CNS. Positive in vivo selection of a brain-adapted strain of SIV resulted in a near-homogeneous strain of virus with distinct properties that may give clues to the viral basis of neuroAIDS.

Original languageEnglish (US)
Article number44
JournalVirology Journal
Volume2
DOIs
StatePublished - May 12 2005

Fingerprint

Viruses
Brain
Genotype
Microglia
nef Genes
Clone Cells
Macrophages
env Genes
Macaca
Encephalitis
Macaca mulatta
HIV Infections
Sequence Analysis
HIV
Phenotype
Amino Acids
Infection

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Development and characterization of positively selected brain-adapted SIV. / Gaskill, Peter J.; Watry, Debbie D.; Burdo, Tricia H.; Fox, Howard S.

In: Virology Journal, Vol. 2, 44, 12.05.2005.

Research output: Contribution to journalArticle

Gaskill, Peter J. ; Watry, Debbie D. ; Burdo, Tricia H. ; Fox, Howard S. / Development and characterization of positively selected brain-adapted SIV. In: Virology Journal. 2005 ; Vol. 2.
@article{0adfd5ae11e049379c3eaf0b80439c11,
title = "Development and characterization of positively selected brain-adapted SIV",
abstract = "HIV is found in the brains of most infected individuals but only 30{\%} develop neurological disease. Both viral and host factors are thought to contribute to the motor and cognitive disorders resulting from HIV infection. Here, using the SIV/rhesus monkey system, we characterize the salient characteristics of the virus from the brain of animals with neuropathological disorders. Nine unique molecular clones of SIV were derived from virus released by microglia cultured from the brains of two macaques with SIV encephalitis. Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR. As this genotype was found in the brains of two separate animals, and it encoded a set of distinct amino acid changes from the infecting virus, it demonstrates the convergent evolution of the virus to a unique brain-adapted genotype. This genotype was distinct from other macrophage-tropic and neurovirulent strains of SIV. Functional characterization of virus derived from representative clones showed a robust in vitro infection of 174xCEM cells, primary macrophages and primary microglia. The infectious phenotype of this virus is distinct from that shown by other strains of SIV, potentially reflecting the method by which the virus successfully infiltrates and infects the CNS. Positive in vivo selection of a brain-adapted strain of SIV resulted in a near-homogeneous strain of virus with distinct properties that may give clues to the viral basis of neuroAIDS.",
author = "Gaskill, {Peter J.} and Watry, {Debbie D.} and Burdo, {Tricia H.} and Fox, {Howard S}",
year = "2005",
month = "5",
day = "12",
doi = "10.1186/1743-422X-2-44",
language = "English (US)",
volume = "2",
journal = "Virology Journal",
issn = "1743-422X",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Development and characterization of positively selected brain-adapted SIV

AU - Gaskill, Peter J.

AU - Watry, Debbie D.

AU - Burdo, Tricia H.

AU - Fox, Howard S

PY - 2005/5/12

Y1 - 2005/5/12

N2 - HIV is found in the brains of most infected individuals but only 30% develop neurological disease. Both viral and host factors are thought to contribute to the motor and cognitive disorders resulting from HIV infection. Here, using the SIV/rhesus monkey system, we characterize the salient characteristics of the virus from the brain of animals with neuropathological disorders. Nine unique molecular clones of SIV were derived from virus released by microglia cultured from the brains of two macaques with SIV encephalitis. Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR. As this genotype was found in the brains of two separate animals, and it encoded a set of distinct amino acid changes from the infecting virus, it demonstrates the convergent evolution of the virus to a unique brain-adapted genotype. This genotype was distinct from other macrophage-tropic and neurovirulent strains of SIV. Functional characterization of virus derived from representative clones showed a robust in vitro infection of 174xCEM cells, primary macrophages and primary microglia. The infectious phenotype of this virus is distinct from that shown by other strains of SIV, potentially reflecting the method by which the virus successfully infiltrates and infects the CNS. Positive in vivo selection of a brain-adapted strain of SIV resulted in a near-homogeneous strain of virus with distinct properties that may give clues to the viral basis of neuroAIDS.

AB - HIV is found in the brains of most infected individuals but only 30% develop neurological disease. Both viral and host factors are thought to contribute to the motor and cognitive disorders resulting from HIV infection. Here, using the SIV/rhesus monkey system, we characterize the salient characteristics of the virus from the brain of animals with neuropathological disorders. Nine unique molecular clones of SIV were derived from virus released by microglia cultured from the brains of two macaques with SIV encephalitis. Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR. As this genotype was found in the brains of two separate animals, and it encoded a set of distinct amino acid changes from the infecting virus, it demonstrates the convergent evolution of the virus to a unique brain-adapted genotype. This genotype was distinct from other macrophage-tropic and neurovirulent strains of SIV. Functional characterization of virus derived from representative clones showed a robust in vitro infection of 174xCEM cells, primary macrophages and primary microglia. The infectious phenotype of this virus is distinct from that shown by other strains of SIV, potentially reflecting the method by which the virus successfully infiltrates and infects the CNS. Positive in vivo selection of a brain-adapted strain of SIV resulted in a near-homogeneous strain of virus with distinct properties that may give clues to the viral basis of neuroAIDS.

UR - http://www.scopus.com/inward/record.url?scp=21744440894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21744440894&partnerID=8YFLogxK

U2 - 10.1186/1743-422X-2-44

DO - 10.1186/1743-422X-2-44

M3 - Article

VL - 2

JO - Virology Journal

JF - Virology Journal

SN - 1743-422X

M1 - 44

ER -