Visna virus is the prototype of the subfamily of nontransforming retroviruses that cause slow infections in vivo, and lytic infections in vitro. In this paper we present the first quantitative single cell analysis of the synthesis of viral nucleic acids, using improved methods of in situ hybridization; we identify early visna virus DNA synthesis as the rate-limiting step in transcription, virus production, and cell death in vitro; and we show that by manipulating the extent of early DNA synthesis we can slow the tempo of infection in vitro from 3 days to 3 weeks.
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We wish to thank H. Lukes for typing the manuscript, and D. Alling for statistical analyses. This work was supported by research funds from the Veterans Administration and by grants from the National Institutes of Health, and the American Cancer Society. Dr. Haase is a Medical Investigator of the Veterans Administration.