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Journal of Virology, October 2007, p. 10669-10679, Vol. 81, No. 19
0022-538X/07/$08.00+0 doi:10.1128/JVI.00517-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Although Macrophage-Tropic Simian/Human Immunodeficiency Viruses Can Exhibit a Range of Pathogenic Phenotypes, a Majority of Isolates Induce No Clinical Disease in Immunocompetent Macaques
Tatsuhiko Igarashi,1
Olivia K. Donau,1
Hiromi Imamichi,2
Yoshiaki Nishimura,1
Theodore S. Theodore,1
Ranjini Iyengar,1
Christopher Erb,1
Alicia Buckler-White,1
Charles E. Buckler,1 and
Malcolm A. Martin1*
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 Science Applications International Corporation—Frederick, Inc., Frederick, Maryland 217022
Received 12 March 2007/ Accepted 3 July 2007
Unlike prototypical lentiviruses like visna and caprine arthritis-encephalitis viruses, which are mainly macrophage tropic (M-tropic), primate lentiviruses primarily target CD4+ T lymphocytes. We previously reported that during the late phase of highly pathogenic chimeric simian/human immunodeficiency virus (SHIV) infections of rhesus macaques, when CD4+ T cells have been systemically eliminated, high levels of viremia are maintained from productively infected macrophages. The availability of several different M-tropic SHIVs from such late-stage immunocompromised animals provided the opportunity to assess whether they might contribute to the immune deficiency induced by their T-cell-tropic parental viruses or possibly cause a distinct disease based on their capacity to infect macrophages. Pairs of rhesus monkeys were therefore inoculated intravenously with six different M-tropic SHIV preparations, and their plasma viral RNA loads, circulating lymphocyte subset numbers, and eventual disease outcomes were monitored. Only one of these six M-tropic SHIVs induced any disease; the disease phenotype observed was the typical rapid, complete, and irreversible depletion of CD4+ T cells induced by pathogenic SHIVs. An analysis of two asymptomatic monkeys, previously inoculated with an M-tropic SHIV recovered directly from alveolar macrophages, revealed that this inoculum targeted alveolar macrophages in vivo, compared to a T-cell-tropic virus, yet no clinical disease occurred. Although one isolate did, in fact, induce the prototypical rapid, irreversible, and complete loss of CD4+ T cells, indicating that M-tropism and pathogenicity may not be inversely related, the majority of M-tropic SHIVs induced no clinical disease in immunocompetent macaques.
* Corresponding author. Mailing address: Laboratory of Molecular Microbiology, Building 4, Room 315, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 496-4012. Fax: (301) 402-0226. E-mail: mmartin{at}niaid.nih.gov
Published ahead of print on 11 July 2007.
Journal of Virology, October 2007, p. 10669-10679, Vol. 81, No. 19
0022-538X/07/$08.00+0 doi:10.1128/JVI.00517-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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