10 May 2003 22:00 GMT
by Julie Clayton
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Denver, Colorado - The surge of HIV that can occur when patients stop their drug treatment, from virtually undetectable to high numbers of virus particles in the blood, reveals the virus's knack for hiding in body tissues, where without replication they remain insensitive to antiretroviral drugs. It now appears that at least one such reservoir - follicular dendritic cells (FDCs) - can trap virus particles for six months or more.
The FDC stash contains virus particles of great genetic diversity, which could contribute significantly to the rebounding viremia if therapy stops, according to Brandon Keele of Brigham Young University in Provo, Utah, who presented his findings here at the 90th anniversary meeting of the American Academy of Immunologists (AAI).
It's a case of FDCs doing what they do best: sequestering antigen in lymph nodes over long periods of time, providing what appears to be a top-up stimulation to T cells and B cells in order to maintain immunological memory of past encounters with invading pathogens. FDCs have long been suspected of harboring HIV, but the extent and diversity of the reservoir that Keele and his colleagues discovered was unexpected.
FDCs were sampled from a variety of tissues, including brain, blood, bone marrow, spleen, and lymph nodes, after the autopsy of four AIDS patients. Keele's team then separated virus-bearing FDCs and also CD4-bearing T cells - a main target for HIV infection - and isolated virus particles that were still capable of infecting cultured cells.
RNA and DNA extraction, followed by PCR amplification of the viral env and pol genes, revealed virus particles on FDCs with four times the genetic diversity than those in any other tissue, demonstrating that FDCs can trap virus over time.
One patient in particular had a detailed clinical history including multiple blood samples being stored for up to 20 months before death. By comparing autopsy samples with these, the researchers detected virus mutants bearing unique drug resistance mutations that appeared around six months before death, which were present only on "archived" virus particles in FDCs.
"Early-on, virus trapped there may end up being more stable than virus that's trapped in high virus environment," said Keele's colleague Gregory Burton. "We think that there are protective mechanisms that allow this to be preserved," he said.