The proteins of lymphocyte- and macrophage-tropic strains of simian immunodeficiency virus are processed differently in macrophages.
Since the pathogenesis of SIVmac disease complex is thought to be explained by the tropism of the infecting virus for either CD4+ T-lymphocytes or macrophages or both types of cells, we compared the infection in primary macaque macrophages with molecularly cloned, lymphocyte-tropic SIVmac239 and a cloned, macrophage-tropic chimeric virus (SIVmac239/17E) whose env gene was derived from brain of a macaque (17E) dying from SIV-induced encephalopathy. SIVmac239/17E caused a productive, syncytial cytopathic infection accompanied by accumulation of virus particles within cytoplasmic vesicles of the macrophages. Pulse-chase and immune precipitation studies showed that both the viral glycoprotein precursor (gp160) and the gag precursor (p57) were cleaved into gp120 and p27, respectively, and both were released into the culture medium of infected cells, although most of the p27 remained cell associated. SIVmac239 also infected macrophages, but in comparison to SIVmac239/17E, minimal virus replication occurred. Immunocytostaining revealed that while occasional syncytia were observed in cultures, the majority of the infected cells were not associated with syncytium formation. Ultrastructural studies did not reveal the accumulation of virions within infected macrophages. Pulse-chase studies showed that both gp160 and p57 were produced but were cleaved inefficiently and only minimal amounts of gp120 and p27 were released into the culture medium, even after prolonged incubation times. The processing of proteins of the two viruses was indistinguishable in lymphocytes. Since these two viruses are identical except for changes within the env gene, these results indicate that efficient assembly and release of SIV from blood-derived macrophages is mediated by changes in the envelope glycoprotein.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, Kansas City 66160-7424.
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Stephens
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McClure
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Narayan
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016521:Electrophoresis, Gel, Pulsed-Field; D006023:Glycoproteins / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism* / Q000821:virology; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D008854:Microscopy, Electron; D011499:Protein Processing, Post-Translational; D015302:Simian Immunodeficiency Virus / Q000378:metabolism* / Q000472:pathogenicity; D014764:Viral Proteins / Q000378:metabolism*
D006023:Glycoproteins; D014764:Viral Proteins