Activation of caprine arthritis-encephalitis virus expression during maturation of monocytes to macrophages

Lentiviruses, which cause arthritis-encephalitis and maedi-visna in goats and sheep, respectively, cause persistent infections in these animals. The viruses replicate productively at low levels in macrophages in diseased organs such as the "maedi lung" and nonproductively in other cell types such as leukocytes in peripheral blood. Nonproductive infections become productive during in vitro cultivation of the cells. This study showed that monocytes were the only cells in the peripheral blood leukocytes of an infected animal in which virus was detected and that virus activation occurred only when these cells matured into macrophages. Only a minute fraction of cultured monocytes matured into macrophages, and viral infectivity was associated exclusively with this fraction. Antiglobulin-coated glass wool fragments were lethal for monocyte macrophages because of toxic phagocytosis, but had no effect on B or T lymphocytes. The simultaneous addition of the glass fragments and leukocytes to culture dishes resulted in no macrophage maturation and no virus production. The addition of the fragments to virus-producing macrophages caused the death of the cells and a decline in virus production. Virus production in less avidly phagocytic cells was unaffected by the glass. Thus, although macrophages may be permissive for virus replication, one mechanism for restricted virus expression in vivo may be physiological factors controlling the maturation of these cells.