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Posted: 1 Aug 2011
30 years in 30 weeks, 1993

Categories: careers, comment, opinion piece

The family of lentiviruses, to which HIV belongs, were named so because they cause slowly progressive diseases after long periods of incubation ((lenti-, Latin for "slow").  Initially, HIV was also believed to remain latent because of the long time that typically separated infection and onset of AIDS.  However, in an important paper published in 1993, Pantaleo et al.  showed that HIV is damaging the lymphoid tissues in an infected person even before the development of immunodeficiency.

HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease.  
Pantaleo, G, C. Graziosi, JF Demarest, L Butini, M Montoni, CH Fox, JM Orenstein, DP Kotler and AS Fauci.
Nature, 362:355-358, 1993.

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1992 < All years > 1994

Commentary by Drs. Giuseppe Pantaleo and Anthony S. Fauci

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The paper entitled ‘HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease’ was published in Nature in 1993 (vol. 362:355-358).  The study, performed before the availability of sensitive assays for plasma viremia, showed that throughout the asymptomatic stage of HIV infection, significant viral activity occurred even during the prolonged period of apparent disease quiescence when patients felt well and damage to the immune system was not yet considered to be severe.  
Because of the lack of sensitive assays for plasma viremia, the study simultaneously compared HIV replication in peripheral blood mononuclear cells and lymphoid tissue (lymph nodes and tonsils were studied) from the same individuals, and demonstrated a striking dichotomy between blood mononuclear cells and lymphoid tissue in viral burden and replication.  This study also shed light on the mechanisms responsible for the higher accumulation and replication of HIV in lymphoid tissues during the early stages of disease.  The mechanisms included a) trapping of HIV virions by the follicular dendritic cell network and b) the sequestration of infected CD4 T cells in hyperplastic lymph nodes.  Furthermore, the study indicated that the lymphoid organs were the critical sites for immune destruction seen in HIV disease.  Importantly, this study prompted us to rethink the concept of clinical latency since the findings clearly demonstrate that immune destruction occurs even during the asymptomatic phase of disease.  
Of note, the concept of significant viral replication as manifested by plasma viremia during the prolonged period of apparent disease quiescence was shown using a competitive polymerase chain reaction assay in a paper published almost simultaneously in 1993 in Science by Piatak et al.  Thus, as a result of our study, it became clear that virus was actively replicating in and being trapped in lymphoid tissue.  As disease progressed in lymphoid tissue, there was progressive destruction of lymphoid architecture.  This occurs during the time that some patients were still considered to be in the clinically latent stage of disease.  In the last sentence of the paper, we indicate that awareness of the potential for lymphoid tissue destruction even during what was considered to be clinical latency could have “important implications in the design of therapeutic strategies”.  Indeed, current therapeutic strategies would call for the administration of anti-retroviral therapy in these patients.  The major message was that a considerable degree of lymphoid tissue damage can occur in HIV-infected individuals at a time when they appear to be clinically well, a concept that is very clear to us today.

About the authors:  Dr. Anthony S. Fauci is director of the National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health.
Dr. Giuseppe Pantaleo is chief of the Division of Immunology and Allergy and chief of the Laboratory of AIDS Immunopathogenesis at the Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne.
 

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