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A non-retroviral RNA virus persists in DNA form

Abstract

Infection of adult mice with lymphocytic choriomeningitis virus (LCMV), a non-cytopathic segmented RNA virus, leads initially to generalized infection, followed by clearance and subsequent lifelong immunity. Indirect evidence has suggested that viral antigens may persist in lymphoid tissues during the phase of immunological memory, but viral genomic RNA has not been detected in previous studies1,2. During a search for persistent virus in the spleen, we identified LCMV-specific sequences present as DNA by polymerase chain reaction (PCR) in mice over 200 days after infection. In vivo and in vitro studies revealed that reverse transcription of viral RNA into complementary DNA occurred after acute infection of cells of its natural hosts, mouse and hamster, but not of other species and could be inhibited in vitro by azidothymidine (AZT), indicating that this was mediated by endogenous reverse transcriptase activity. These findings reveal a surprising and new pathway of interaction between exogenous RNA viruses and endogenous retroviral, and perhaps other host components, that results in the persistence of virally determined DNA. We speculate that the latter may function in vivo as a form of DNA vaccine.

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Figure 1: Identification of LCMV-derived DNA after infection in vivo.
Figure 2: Analysis of LCMV DNA production in vitro.
Figure 3: Persistence of LCMV-specific DNA in cells after acute infection.

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Acknowledgements

This work was supported by the Wellcome Trust, the Swiss National Foundation for Science and the Kanton of Zurich, Switzerland. We thank E. Horvath, H. Krettli, A. Oxenius, S. Oehen, K.Riem, O. Planz, P. Seiler, N. Wey, D. Zimmerman and his group and J. Schupbach and J. Boeni of the Swiss National Centre for Retroviruses, University of Zurich for their technical help; we also thank L.Stitz (BFAV, Tübingen) and J. Klein (MPI, Tübingen) for providing mice and D.Bishop, J. Goudsmit, M.Billeter and R. Cattaneo for helpful discussions.

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Correspondence to Rolf M. Zinkernagel.

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Klenerman, P., Hengartner, H. & Zinkernagel, R. A non-retroviral RNA virus persists in DNA form. Nature 390, 298–301 (1997). https://doi.org/10.1038/36876

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