Two research teams are publishing reports today in the journalNature showing that HIV thrives hidden within the lymphsystem long before symptoms of AIDS appear.
The reports imply that anti-viral drugs should be given beforepatients show drops in helper T cells associated in later stagesof disease, and that other therapeutic approaches should be re-evaluated.
Anthony Fauci, director and chief of the Laboratory ofImmunoregulation of the National Institutes of Health, andAshley Haase of the University of Minnesota showed that inlymph tissues large numbers of virus particles are trappedwhere they are ready to infect circulating T cells.
Lymph tissues include the lymph nodes, spleen, tonsils,adenoids and other organs. Immune activity is concentrated inregions called germinal centers within these tissues, wherethread-like tentacles of follicular dendritic cells form networksthat trap invaders and present them to immune cells thatcongregate there.
It is on these follicular dendritic cells that virus particles werespotted through electron microscopy. Fauci's group found inlymph node biopsies from various organs of 12 patients atdifferent stages of infection that the networks break down inlate-stage disease and virus trapping is impaired, allowingspillover of large quanities of virus into the bloodstream.
In fact, the group simultaneously tracked virus levels in theblood via amplification of viral RNA in mononuclear cells andfound five to 10 more infected cells in lymph tissue in earlystages of disease.
"In patients in the so-called clinically latent stage of HIVinfection, we found low viral burden and replication in thebloodstream, but higher levels of virus and replication in thelymphoid tissues," said lead author Giuseppe Pantaleo, avisiting scientist at NIH's Laboratory of Immunoregulation."Our studies suggest that the lymphoid organs, and not thebloodstream, are the critical sites of the immune destructionseen in HIV disease."
Haase's group found "an extraordinarily large number" oflatently infected white blood cells in the lymph system in thelymph tissue of three HIV-positive patients, presumed to nothave AIDS symptoms, who died of drug overdoses, as well asbiopsied tissue from one patient being treated with AZT.
The studies show that up to a third of CD4-bearing T cells inlymph nodes appear to be infected, and the virus is activelyreplicating in about one in 100 to 400 virus-infected T cells.
"We must rethink the concept of clinical latency," Fauci said."The new findings demonstrate that significant viral activityoccurs even during the prolonged period of apparent diseasequiescence, when patients feel well and damage to the immunesystem is not yet severe. This information may prompt arethinking of the optimal time to initiate treatment of HIV-infected patients."
The researchers speculate that HIV begins replicating anddestroys the T cells it inhabits when the cells are activated bythe immune system protein cytokines in response to aninfecting organism. After the HIV-infected person hasencountered many infections, the total number of T cells drops,indicating a late stage of HIV infection.
In an opinion piece accompanying the reports, physicians DaniBolonesi of Duke University Medical Center in Durham, N.C., andHoward Temin at the McArdle Laboratory for Cancer Researchconcluded, "A clear message from this new work is that HIVinfection is a very complicated process and that it will requirethe march of science, frustratingly slow as it sometimes seems,to gain sufficient knowledge to control it."
-- Nancy Garcia Associate Editor
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