Researchers at the Institute of Human Virology of the University of
Maryland School of Medicine have identified a new behavior for the human
macrophage that provides new explanations for several features of HIV
biology, including how the virus persists within the body indefinitely,
how quiescently infected CD4+ T-cells arise, and how the infection leads
to depletion of CD4+ T-cells. The research team found that macrophages
cultured from human blood can function as "nurse cells" and in this
capacity, generate and release newly formed cells. The new cells
released include a previously unknown small cell, termed "self-renewing
monocytoid cell" (SRMC) that is highly susceptible to infection with
HIV. This small cell can develop into another nurse macrophage that can,
in turn, produce another small cell. This nurse macrophage/small cell
developmental cycle can continue in culture for several generations,
even during continuous production of HIV. Current anti-HIV drugs cannot
inhibit HIV maintained through this process, because they act to prevent
new infection. The nurse macrophage/small cell cycle does not require
infection of new cells and for this reason, it may help to explain,
along with latently infected long-lived cells, how "wildtype" HIV
strains -- those lacking drug resistance mutations -- are maintained
within the body during years of uninterrupted anti-HIV therapy. The
researchers emphasize that although working with HIV led them to
recognize nurse macrophage behavior, all of the phenomena observed can
be seen in uninfected, as well as HIV-infected macrophage cultures.