This finding has several important implications, according to
investigators Dr. Jan Orenstein from George Washington University
and Dr. Sharon Wahl from the National Institute of Dental Research.
"Preventing or eliminating opportunistic infections is not
only essential to the immediate well-being of the patient, but
can also slow the cycle of virus production that leads to further
immune system damage," said Dr. Wahl. "The macrophage
appears to be a key player in this scenario by functioning as
a long-lived reservoir of virus production. "
It has been known for some time that CD4 T cells are the primary
target of HIV infection, and that their destruction leads to a
weakened immune system and susceptibility to "opportunists"-microorganisms
that normally don't infect a healthy individual. As HIV infection
progresses toward AIDS, the CD4 T cells are the chief source of
new virus, creating a cycle of escalating virus production and
T cell death. The paradox has been how the levels of HIV continue
to increase over the course of AIDS, at the same time the T cell
population dramatically decreases.
Drs. Orenstein and Wahl thought macrophages might hold the answer
to this riddle. Macrophages are immune cells that roam throughout
the tissues for periods from months to perhaps years, seeking
out and destroying invading organisms. The scientists knew that
macrophages could be infected with HIV, but these voracious scavengers
were not thought to be a significant source of virus production.
Close examination of lymph nodes from AIDS patients infected with
a variety of common opportunists, including Pneumocystis carinii
and Mycobacterium avium, proved otherwise. These patients
not only had from 5 to over 100 times the number of virus-producing
macrophages found in the nodes of opportunist-free HIV patients,
the individual macrophages also demonstrated a much higher level
of virus production.
The actual mechanism that switches macrophages from HIV carriers
to producers is not yet known. Opportunistic microorganisms apparently
act as a magnet, say the investigators, pulling together large
numbers of both HIV-infected and uninfected macrophages. The
opportunists then in some way stimulate the HIV-infected macrophages
to produce virus, which ultimately spreads to uninfected macrophages
and T cells.
The members of the research team were Dr. Jan Orenstein, George
Washington University, Washington, DC; Dr. Cecil Fox, Molecular
Histology, Inc., Gaithersburg, MD; and Dr. Sharon Wahl, National
Institute of Dental Research, National Institutes of Health, Bethesda,