UNIQUE LENTIVIRUS HOST INTERACTIONS - SIVSMMPBJ14 INFECTION OF MACAQUES

The most virulent primate lentivirus identified to date, the simian virus SIVsmmPBj14 (SiV-PBj14), is unique not only because it causes acute disease and death within days instead of months or years, but also because of its replicative and cellular activation properties. The acute disease syndrome has many features in common with primary HIV-1 disease, but differences in the respective outcomes of these two acute lentiviral infections appear to be linked to the rapidity with which SIV-PBj14 replicates and the high titers of virus that subsequently accumulate in lymphoid tissues. The most prominent pathologic feature of SIV-PBj14 is extensive lymphoid hyperplasia of T-cell zones, especially in the gut-associated lymphoid tissue. These expanded T-cell zones contain a high proportion of lymphoblasts, activated macrophages and syncytial cells, which are positively correlated with high numbers of SIV antigen-positive cells. Replication of the virus to high titers, accompanied by extensive cellular activation and proliferation, leading to high levels of cytokines, such as interleukin-6 and tumor necrosis factor-alpha, are consistent with acute inflammatory disease. The pathogenesis of SIV-PBj14 also appears to correlate most directly with some of its unique biologic properties, such as the ability to replicate in resting peripheral blood mononuclear cells, to activate lymphocytes, and to induce lymphocyte proliferation. Biologically and molecularly cloned viruses derived from SIV-PBj14 and isolates obtained from macaque PBj at earlier times, are being used to identify viral determinants that influence biologic and pathogenic properties of SIV-PBj14. Further characterization of this virus should provide new insights into lentivirus-cell interactions and their contributions to disease.