Nature 362, 355 - 358 (25 March 1993); doi:10.1038/362355a0

HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease

Giuseppe Pantaleo^*, Cecilia Graziosi^*, James F. Demarest^*, Luca Butini^†, Maria Montroni^†, Cecil H. Fox^‡, Jan M. Orenstein^§, Donald P. Kotler & Anthony S. Fauci^*

^*Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
^†Department of Internal Medicine, University of Ancona, 60020 Ancona, Italy
^‡Department of Neuropathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
^§Department of Pathology, George Washington University, Washington DC 20037, USA
St Luke's-Roosevelt Hospital Center, New York, New York 10025, USA

PRIMARY infection with the human immunodeficiency virus (HIV) is generally followed by a burst of viraemia with or without clinical symptoms^1–3. This in turn is followed by a prolonged period of clinical latency. During this period there is little, if any, detectable viraemia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells⁴. We have analysed viral burden and levels of virus replication simultaneously in the blood and lymphoid organs of the same individuals at various stages of HIV disease. Here we report that in early-stage disease there is a dichotomy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency, even at times when minimal viral activity is demonstrated in blood.

References

1.	Daar, E. S., Moudgil, T., Meyer, R. D. & Ho, D. D. New Engl. J. Med. 324, 961−964 (1991). | PubMed | ChemPort |
2.	Clark, S. J. et al. New Engl. J. Med. 324, 954−960 (1991). | PubMed | ChemPort |
3.	Tindall, B. & Cooper, D. A. AIDS 5, 1−14 (1991). | PubMed | ISI | ChemPort |
4.	Fauci, A. S., Schnittman, S. M., Poll, G., Koenig, S. & Pantaleo, G. Ann. Intern. Med. 114, 678−693 (1991). | PubMed | ChemPort |
5.	Pantaleo, G. et al. Proc. natn. Acad. Sci. U.S.A. 88, 9838−9842 (1991). | ChemPort |
6.	Folks, T. M. et al. J. exp. Med. 164, 280−290 (1986). | Article | PubMed | ISI | ChemPort |
7.	Michael, N. L., Vahey, M., Burke, D. S. & Redfield, R. R. J. Virol. 66, 310−316 (1992). | PubMed | ISI | ChemPort |
8.	Fox, C. H. et al. J. infect. Dis. 164, 1051−1057 (1991). | PubMed | ISI | ChemPort |
9.	Racz, P. et al. Prog. Allergy 37, 81−181 (1986). | PubMed | ChemPort |
10.	Armstrong, J. A., Dawkins, R. L. & Home, R. Immun. Today 6, 121−122 (1985).
11.	Biberfeld, P. et al. Acta path. microbiol. immun. scand. 95, 47−65 (1987). | ChemPort |
12.	Armstrong, J. A. in Accessory Cells in HIV and Other Retroviral Infections (eds Racz, P., Dijkstra, C. D. & Gluckman, J. C.) 69−82 (Karger, Basel, 1991).
13.	Spiegel, H., Herbst, H., Niedobitek, G., Foss, H. D. & Stein, H. Am. J. Path. 140, 15−22 (1992). | PubMed | ChemPort |
14.	Emilie, D. et al. J. clin. Invest. 86, 148−159 (1990). | PubMed | ISI | ChemPort |
15.	Tenner-Racz, K., Racz, P., Dietrich, M. & Karin, P. Lancet i, 105−106 (1985).
16.	Haynes, B. F. in AIDS Etiology, Diagnosis, Treatment and Prevention (eds Devita, V. T. Jr et al.) 77−86 (Lippincott, Philadelphia, 1992).
17.	Volberding, P. A. et al. New Engl. J. Med. 322, 941−949 (1990). | PubMed | ChemPort |
18.	Clouse, K. A. et al. J. Immun. 142, 431−438 (1989). | PubMed | ChemPort |
19.	Graziosi, C., Pantaleo, G. & Fauci, A. S. Curr. Protoc. Immun. (in the press).
20.	Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156−159 (1987). | Article | PubMed | ISI | ChemPort |
21.	Kwok, S. et al. J. Virol. 61, 1690−1694 (1987). | PubMed | ISI | ChemPort |
22.	Ou, C. Y. et al. Science 239, 295−297 (1988). | PubMed | ISI | ChemPort |
23.	Schnittman, S. M., Greenhouse, J. J., Lane, H. C., Pierce, P. F. & Fauci, A. S. AIDS Res. Hum. Retrovir. 7, 361−367 (1991). | PubMed | ChemPort |