1887

Abstract

Previous studies have suggested that monocytes or macrophages may mediate internal virus spread. For the present study, the tissue distribution and infectious potential of dye-labelled and/or lactate dehydrogenase-elevating virus (LDV)-infected murine macrophages were determined. Murine peritoneal macrophages were labelled with the fluorescent carbocyanine tracking dye Dil, injected into mice, and the tissue distribution of Dil-labelled cells was determined by fluorescence analysis of frozen sections. Mice receiving intravenous (i.v.) or intraperitoneal injections of Dil-labelled macrophages displayed rapid and broad tissue distribution of the labelled cells. Intravaginal injection of Dil-labelled macrophages resulted in penetration into the placentas, but not the fetuses, of pregnant mice. When macrophages were LDV-infected and Dil-labelled prior to i.v. injection into pregnant mice, they homed to various tissues including the placenta, but were not found in fetuses. Intravaginal injection of LDV-infected macrophages resulted in systemic LDV infection, even though the free-virus dose was less than the minimum infectious dose by this route. Neither polyclonal nor monoclonal IgG anti-LDV antibodies protected mice from vaginal infection with cell-associated virus, and LDV-immune complexes were themselves infectious by the vaginal route. These results show that exogenous macrophages are widely distributed following parenteral injection, penetrate locally to placentas after intravaginal injection, and are capable of acting vaginally as relatively efficient virus infection-delivery vehicles. Thus, ‘Trojan Horse’ macrophages are potentially infectious vehicles both for internal virus spread and for animal-to-animal transmission.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-12-3005
1996-12-01
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/12/JV0770123005.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-12-3005&mimeType=html&fmt=ahah

References

  1. Anderson G. W., Rowland R. R. R., Palmer G. A., Even C., Plagemann P. G. W. 1995; Lactate dehydrogenase-elevating virus replication persists in liver, spleen, lymph node, and testis tissues and results in accumulation of viral RNA in germinal centers, concomitant with polyclonal activation of B cells. Journal of Virology 69:5177–5185
    [Google Scholar]
  2. Broen J., Bradley D. S., Powell K. M., Cafruny W. A. 1992; Immune regulation of maternal–fetal virus transmission in SCID mice infected with lactate dehydrogenase-elevating virus. Viral Immunology 5:133–140
    [Google Scholar]
  3. Cafruny W. A., Plagemann P. G. W. 1982a; Immune response to lactate dehydrogenase-elevating virus: isolation of infectious virus- immunoglobulin G complexes and quantitation of specific anti-viral immunoglobulin G response in wild-type and nude mice. Infection and Immunology 37:1001–1006
    [Google Scholar]
  4. Cafruny W. A., Plagemann P. G. W. 1982b; Immune response to lactate dehydrogenase-elevating virus: serologically specific rabbit neutralizing antibody to the virus. Infection and Immunity 37:1007–1012
    [Google Scholar]
  5. Cafruny W. A., Hovinen D. E. 1988; The relationship between route of infection and minimum infectious dose: studies with lactate dehydrogenase-elevating virus. Journal of Virological Methods 20:265–268
    [Google Scholar]
  6. Cafruny W. A., Chan S. P. K., Harty J. T., Yousefi S., Kowalehyk K., McDonald D., Forman B., Budweg G., Plagemann P. G. W. 1986; Antibody response of mice to lactate dehydrogenase-elevating virus during infection and immunization with inactivated virus. Virus Research 5:357–375
    [Google Scholar]
  7. Cafruny W. A., Bradley S. E., Brunick A., Nelson D. M., Nelson R. F. 1996; Determination of the viremia threshold for dental crossinfection in a mouse model. Journal of Virological Methods 59:83–89
    [Google Scholar]
  8. Harty J. T., Plagemann P. G. W. 1988; Formalin inactivation of the lactate dehydrogenase-elevating virus reveals a major neutralizing epitope not recognized during natural infection. Journal of Virology 62:3210–3216
    [Google Scholar]
  9. Haven T. R., Rowland R. R. R., Plagemann P. G. W., Wong G. H. W., Bradley S. E., Cafruny W. A. 1996; Regulation of transplacental virus infection by developmental and immunological factors: studies with lactate dehydrogenase-elevating virus. Virus Research 41:153–161
    [Google Scholar]
  10. Hom R. C., Soman G., Finberg R. 1989; Trojan horse lymphocytes: a vesicular stomatitis virus-specific T-cell clone lyses target cells carrying the virus. Journal of Virology 63:4157–4164
    [Google Scholar]
  11. King W. W., St Amant L. G., Lee W. R. 1994; A technique for serial spermatozoa collection in mice. Laboratory Animal Science 44:295–296
    [Google Scholar]
  12. Levy J. A. 1988; The transmission of AIDS: the case of the infected cell. Journal of the American Medical Association 259:3037–3038
    [Google Scholar]
  13. Meredith M. J. 1993 Porcine Reproductive and Respiratory Syndrome 7th edn Cambridge: Cambridge University Press;
    [Google Scholar]
  14. Peluso R., Haase A., Stowring L., Edwards M., Ventura P. 1985; A Trojan horse mechanism for the spread of Visna virus in monocytes. Virology 147:231–236
    [Google Scholar]
  15. Plagemann P. G. W., Moennig V. 1992; Lactate dehydrogenase- elevating virus, equine arteritis virus, and simian hemorrhagic fever virus: a new group of positive-strand RNA viruses. Advances in Virus Research 41:99–102
    [Google Scholar]
  16. Plagemann P. G. W., Rowland R. R. R., Even C., Faaberg K. S. 1995; Lactate dehydrogenase-elevating virus: an ideal persistent virus?. Seminars in Immunopathology 17:167–186
    [Google Scholar]
  17. Rosen H., Gordon S. 1990; Adoptive transfer of fluorescence- labeled cells shows that resident peritoneal macrophages are able to migrate into specialized lymphoid organs and inflammatory sites in the mouse. European Journal of Immunology 20:1251–1258
    [Google Scholar]
  18. Rugh R. 1969; The Mouse. Its Reproduction and Development Minneapolis: Burgess Publishing;
    [Google Scholar]
  19. Sabin A. B. 1991; Effectiveness of AIDS vaccines. Science 251:1161
    [Google Scholar]
  20. Sabin A. B. 1992; Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry. Proceedings of the National Academy of Sciences, USA 89:8852–8855
    [Google Scholar]
  21. Stueckemann J. A., Holth M., Swart W. J., Kowalehyk K., Smith M. S., Wolstenholme A. J., Cafruny W. A., Plagemann P. G. W. 1982; Replication of lactate dehydrogenase-elevating virus in macrophages. 2. Mechanism of persistent infection in mice and cell culture. Journal of General Virology 59:263–272
    [Google Scholar]
  22. Timony P. J., McCollum W. H. 1993; Equine viral arteritis. Veterinary Clinics of North America Equine Practice 9:295–309
    [Google Scholar]
  23. Ward R. L., Akin E. W. 1984; Minimum infective dose of animal viruses. CRC Critical Reviews in Environmental Control 14:297–310
    [Google Scholar]
  24. Williams A. E., Blakemore W. F. 1990; Monocyte-mediated entry of pathogens into the central nervous system. Neuropathology and Applied Neurobiology 16:377–392
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-12-3005
Loading
/content/journal/jgv/10.1099/0022-1317-77-12-3005
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error