Abstract
Latency is an integral feature of the pathogenesis of cytomegalovirus infection and disease. Using in situ hybridization, we detected viral DNA in the splenic stroma of mice with acute murine cytomegalovirus (MCMV) infection but could not detect latent infection. By using enzymatic amplification of a 700-bp region of exon 4 of immediate-early gene 1 of MCMV, viral DNA was consistently detected in whole spleens of latently infected mice. MCMV DNA was detected in 16 of 23 stromal cell fractions from latently infected animals, in only 2 of 13 residual nonstromal cell fractions, and in none of 9 additional lymphocyte or macrophage-enriched nonstromal cell preparations. We conclude that MCMV DNA is maintained predominantly, and possibly exclusively, in stromal cells in the spleens of latently infected mice.
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Selected References
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- Brautigam A. R., Dutko F. J., Olding L. B., Oldstone M. B. Pathogenesis of murine cytomegalovirus infection: the macrophage as a permissive cell for cytomegalovirus infection, replication and latency. J Gen Virol. 1979 Aug;44(2):349–359. doi: 10.1099/0022-1317-44-2-349. [DOI] [PubMed] [Google Scholar]
- Cheung K. S., Lang D. J. Transmission and activation of cytomegalovirus with blood transfusion: a mouse model. J Infect Dis. 1977 May;135(5):841–845. doi: 10.1093/infdis/135.5.841. [DOI] [PubMed] [Google Scholar]
- Chou S. W. Acquisition of donor strains of cytomegalovirus by renal-transplant recipients. N Engl J Med. 1986 May 29;314(22):1418–1423. doi: 10.1056/NEJM198605293142205. [DOI] [PubMed] [Google Scholar]
- Dutko F. J., Oldstone M. B. Murine cytomegalovirus infects spermatogenic cells. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2988–2991. doi: 10.1073/pnas.76.6.2988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirasawa Y., Tokuhiro H. Electron microscopic studies on the normal human spleen: especially on the red pulp and the reticulo-endothelial cells. Blood. 1970 Feb;35(2):201–212. [PubMed] [Google Scholar]
- Jordan M. C. Adverse effects of cytomegalovirus vaccination in mice. J Clin Invest. 1980 Apr;65(4):798–803. doi: 10.1172/JCI109730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jordan M. C., Jordan G. W., Stevens J. G., Miller G. Latent herpesviruses of humans. Ann Intern Med. 1984 Jun;100(6):866–880. doi: 10.7326/0003-4819-100-6-866. [DOI] [PubMed] [Google Scholar]
- Jordan M. C. Latent infection and the elusive cytomegalovirus. Rev Infect Dis. 1983 Mar-Apr;5(2):205–215. doi: 10.1093/clinids/5.2.205. [DOI] [PubMed] [Google Scholar]
- Jordan M. C., Mar V. L. Spontaneous activation of latent cytomegalovirus from murine spleen explants. Role of lymphocytes and macrophages in release and replication of virus. J Clin Invest. 1982 Oct;70(4):762–768. doi: 10.1172/JCI110672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jordan M. C., Shanley J. D., Stevens J. G. Immunosuppression reactivates and disseminates latent murine cytomegalovirus. J Gen Virol. 1977 Nov;37(2):419–423. doi: 10.1099/0022-1317-37-2-419. [DOI] [PubMed] [Google Scholar]
- Jordan M. C., Takagi J. L., Stevens J. G. Activation of latent murine cytomegalovirus in vivo and in vitro: a pathogenetic role for acute infection. J Infect Dis. 1982 May;145(5):699–705. doi: 10.1093/infdis/145.2.699. [DOI] [PubMed] [Google Scholar]
- Keil G. M., Ebeling-Keil A., Koszinowski U. H. Sequence and structural organization of murine cytomegalovirus immediate-early gene 1. J Virol. 1987 Jun;61(6):1901–1908. doi: 10.1128/jvi.61.6.1901-1908.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klotman M. E., Henry S. C., Greene R. C., Brazy P. C., Klotman P. E., Hamilton J. D. Detection of mouse cytomegalovirus nucleic acid in latently infected mice by in vitro enzymatic amplification. J Infect Dis. 1990 Feb;161(2):220–225. doi: 10.1093/infdis/161.2.220. [DOI] [PubMed] [Google Scholar]
- Klotman M. E., Starnes D., Hamilton J. D. The source of murine cytomegalovirus in mice receiving kidney allografts. J Infect Dis. 1985 Dec;152(6):1192–1196. doi: 10.1093/infdis/152.6.1192. [DOI] [PubMed] [Google Scholar]
- Mayo D., Armstrong J. A., Ho M. Activation of latent murine cytomegalovirus infection: cocultivation, cell transfer, and the effect of immunosuppression. J Infect Dis. 1978 Dec;138(6):890–896. doi: 10.1093/infdis/138.6.890. [DOI] [PubMed] [Google Scholar]
- Mercer J. A., Wiley C. A., Spector D. H. Pathogenesis of murine cytomegalovirus infection: identification of infected cells in the spleen during acute and latent infections. J Virol. 1988 Mar;62(3):987–997. doi: 10.1128/jvi.62.3.987-997.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olding L. B., Jensen F. C., Oldstone M. B. Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction. J Exp Med. 1975 Mar 1;141(3):561–572. doi: 10.1084/jem.141.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pomeroy C., Kline S., Jordan M. C., Filice G. A. Reactivation of Toxoplasma gondii by cytomegalovirus disease in mice: antimicrobial activities of macrophages. J Infect Dis. 1989 Aug;160(2):305–311. doi: 10.1093/infdis/160.2.305. [DOI] [PubMed] [Google Scholar]
- Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
- Shanley J. D., Jordan M. C., Cook M. L., Stevens J. G. Pathogenesis of reactivated latent murine cytomegalovirus infection. Am J Pathol. 1979 Apr;95(1):67–80. [PMC free article] [PubMed] [Google Scholar]
- Shanley J. D., Jordan M. C., Stevens J. G. Modification by adoptive humoral immunity of murine cytomegalovirus infection. J Infect Dis. 1981 Feb;143(2):231–237. doi: 10.1093/infdis/143.2.231. [DOI] [PubMed] [Google Scholar]
- Stagno S., Pass R. F., Dworsky M. E., Henderson R. E., Moore E. G., Walton P. D., Alford C. A. Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection. N Engl J Med. 1982 Apr 22;306(16):945–949. doi: 10.1056/NEJM198204223061601. [DOI] [PubMed] [Google Scholar]
- Stevens J. G. Human herpesviruses: a consideration of the latent state. Microbiol Rev. 1989 Sep;53(3):318–332. doi: 10.1128/mr.53.3.318-332.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tegtmeier G. E. Cytomegalovirus and blood transfusion. Prog Clin Biol Res. 1985;182:175–199. [PubMed] [Google Scholar]
- Williams J. F. Optimization strategies for the polymerase chain reaction. Biotechniques. 1989 Jul-Aug;7(7):762–769. [PubMed] [Google Scholar]
- Wilson E. J., Medearis D. N., Jr, Barrett L. V., Rubin R. H. Activation of latent murine cytomegalovirus in cardiac explant and cell cultures. J Infect Dis. 1985 Sep;152(3):625–626. doi: 10.1093/infdis/152.3.625. [DOI] [PubMed] [Google Scholar]
- Wise T. G., Manischewitz J. E., Quinnan G. V., Aulakh G. S., Ennis F. A. Latent cytomegalovirus infection of BALB/c mouse spleens detected by an explant culture technique. J Gen Virol. 1979 Aug;44(2):551–556. doi: 10.1099/0022-1317-44-2-551. [DOI] [PubMed] [Google Scholar]