Nature Medicine
3, 218 - 221 (1997)
doi:10.1038/nm0297-218
A new approach to investigating the relationship between productive infection and cytopathicity in vivoTodd A. Reinhart1, Michael J. Rogan1, Gregory A. Viglianti2, Dianne M. Rausch3, Lee E. Elden3
& Ashley T. Haase1, 4
1Department of Microbiology, University of Minnesota Medical School, Box 196, 420 Delaware Street SE, Minneapolis, Minnesota 55455, USA
2Department of Microbiology, Boston University School of Medicine, 80 South Concord Street, Boston, Massachusetts 02118, USA
3Laboratory of Cell Biology, National Institute of Mental Health, Building 36, Room 3A17,Bethesda, Maryland 02815, USA
4Correspondence should be addressed to A.T.H. We describe a novel experimental approach to analyzing virus-host relationships and potential mechanisms of cytopathicity in vivo in simian immunodeficiency virus (SIV) infections. Progressive destruction of lymphoid tissue in the course of infection by SIV or human immunodeficiency virus (HIV) accompanies the loss of CD4+ T lymphocytes and sets the stage for AIDS1,2. Because one of the important early events in this pathological process is lysis of follicular dendritic cells3 (FDCs), we investigated the controversial role of productive SIV infection in the destruction of FDCs. To differentiate productive infections from the known association of virus with FDCs as immune complexes trapped on cell surfaces4−6, we used detection of spliced viral mRNAs in cells as evidence of productive infection. We found that spliced and unspliced viral RNAs could be detected by in situ hybridization (ISH) with specific antisense oligonucleotide probes in lymphocytes and macrophages with sensitivities of fewer than ten copies of spliced viral RNA per cell. We detected only unspliced RNA in germinal centers where FDCs reside. Thus, no productive infection of these cells can be detected in vivo by this assay, and their destruction likely occurs by indirect mechanisms that have yet to be determined.
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