Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4 + T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 2 - Trang 658-663 - 2001
Tatsuhiko Igarashi1, Charles R. Brown1, Yasuyuki Endo1, Alicia Buckler‐White1, Ronald J. Plishka1, Norbert Bischofberger1, Vanessa M. Hirsch1, Malcolm A. Martin1
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460; and Gilead Sciences, Inc., Foster City, CA 94404

Tóm tắt

The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chimeric virus SHIV DH12R induces a systemic depletion of CD4 + T lymphocytes in rhesus monkeys during the initial 3–4 weeks of infection. Nonetheless, high levels of viral RNA production continue unabated for an additional 2–5 months. In situ hybridization and immunohistochemical analyses revealed that tissue macrophage in the lymph nodes, spleen, gastrointestinal tract, liver, and kidney sustain high plasma virus loads in the absence of CD4 + T cells. Quantitative confocal immunofluorescence analysis indicated that greater than 95% of the virus-producing cells in these tissues are macrophage and less than 2% are T lymphocytes. Interestingly, the administration of a potent reverse transcriptase inhibitor blocked virus production during the early T cell phase but not during the later macrophage phase of the SHIV DH12R infection. When interpreted in the context of HIV-1 infections, these results implicate tissue macrophage as an important reservoir of virus in vivo . They become infected during the acute infection, gradually increase in number over time, and can be a major contributor to total body virus burden during the symptomatic phase of the human infection.

Từ khóa


Tài liệu tham khảo

10.1056/NEJM199709113371102

10.1056/NEJM199803263381301

10.1016/S0140-6736(05)76156-0

10.1056/NEJM199905273402102

10.1056/NEJM199905273402101

10.1001/jama.282.17.1627

10.1073/pnas.94.24.13193

10.1126/science.278.5341.1295

10.1126/science.278.5341.1291

10.1073/pnas.96.26.15109

10.1038/77481

10.1172/JCI10565

10.1073/pnas.96.24.14049

Guide for the Care and Use of Laboratory Animals, revised Ed. (National Institutes of Health, Department of Health and Human Services, Washington, DC, publication no. (NIH) 85–23. (1985).

10.1128/JVI.74.15.6935-6945.2000

10.1086/514053

10.1128/jvi.69.2.955-967.1995

10.1128/jvi.71.2.1608-1620.1997

10.1126/science.270.5239.1197

10.1089/aid.1997.13.707

10.1128/JVI.72.5.4265-4273.1998

10.1126/science.3014648

10.1089/aid.1990.6.967

10.1126/science.276.5320.1857

S Aquaro, E Balestra, A Cenci, M Francesconi, R Calio, C F Perno J Biol Regul Homeost Agents 11, 69–73 (1997).

10.1002/jmv.1890290306

10.1084/jem.168.3.1111

10.1002/jlb.56.3.381

10.1002/jlb.62.1.138

10.1086/515642

10.1089/aid.1989.5.397

10.1128/jvi.70.10.6922-6928.1996

10.1128/jvi.70.5.3189-3197.1996

10.1073/pnas.83.18.7089

10.1126/science.3016903

10.1212/WNL.42.9.1736

10.1093/infdis/158.1.193

10.1212/WNL.40.2.323

10.1126/science.286.5443.1353

10.1128/jvi.68.7.4409-4419.1994

10.1128/JVI.74.14.6418-6424.2000

10.1128/jvi.67.4.2182-2190.1993

10.1038/387188a0

10.1016/S0140-6736(94)91222-X

10.1097/00002030-199201000-00008

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 2

658-663

Thông tin tác giả