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Journal of Virology, March 2001, p. 2262-2275, Vol. 75, No. 5
Department of Virology and Immunology,
Southwest Foundation for Biomedical Research, San Antonio, Texas
78227,1 and Emory Vaccine Center and
Emory/Atlanta Center for AIDS Research, Emory University School of
Medicine, Atlanta, Georgia 303292
Received 11 September 2000/Accepted 7 December 2000
African green monkeys can maintain long-term persistent infection
with simian immunodeficiency viruses (SIVagm) without developing AIDS
and thus provide an important model for understanding mechanisms of
natural host resistance to disease. This study assessed the levels and
anatomic distribution of SIVagm in healthy, naturally infected monkeys.
Quantitative competitive reverse transcriptase PCR assays developed to
measure SIVagm from two African green monkey subspecies demonstrated
high levels of SIV RNA in plasma (>6 × 106 RNA
copies/ml) in sabaeus and vervet monkeys. Infectious virus was readily
recovered from plasma and peripheral blood mononuclear cells and shown
to be highly cytopathic in human cell lines and macrophages. SIVagm DNA
levels were highest in the gastrointestinal tract, suggesting that the
gut is a major site for SIVagm replication in vivo. Appreciable levels
of virus were also found within the brain parenchyma and the
cerebrospinal fluid (CSF), with lower levels detected in peripheral
blood cells and lymph nodes. Virus isolates from the CSF and brain
parenchyma readily infected macrophages in culture, whereas lymph node
isolates were more restricted to growth in human T-cell lines.
Comparison of env V2-C4 sequences showed extensive amino
acid diversity between SIVagm recovered from the central nervous system
and that recovered from lymphoid tissues. Homology between brain and
CSF viruses, macrophage tropism, and active replication suggest
compartmentalization in the central nervous system without associated
neuropathology in naturally infected monkeys. These studies provide
evidence that the nonpathogenic nature of SIVagm in the natural host
can be attributed neither to more effective host control over viral
replication nor to differences in the tissue and cell tropism from
those for human immunodeficiency virus type 1-infected humans or
SIV-infected macaques.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2262-2275.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Simian Immunodeficiency Virus Replicates to High
Levels in Naturally Infected African Green Monkeys without Inducing
Immunologic or Neurologic Disease
*
Corresponding author. Mailing address: Southwest
Foundation for Biomedical Research, Department of Virology and
Immunology, 7620 N.W. Loop 410 at Military Drive, San Antonio, TX
78227. Phone: (210) 258-9475. Fax: (210) 670-3332. E-mail:
jallan{at}icarus.sfbr.org.
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