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. 1997 Jan;71(1):755–758. doi: 10.1128/jvi.71.1.755-758.1997

Antibody prevents the establishment of persistent arenavirus infection in synergy with endogenous T cells.

J R Baldridge 1, T S McGraw 1, A Paoletti 1, M J Buchmeier 1
PMCID: PMC191113  PMID: 8985412

Abstract

A cardinal feature of the biology of lymphocytic choriomeningitis virus (LCMV) is its ability to establish persistent infections in mice. Persistence is usually established by infection of the mouse during the in utero or neonatal period. Susceptibility can be extended to the adult by treatment with immunosuppressive agents or by infection with immunosuppressive strains of LCMV. In this study we investigated the capacity of passively acquired anti-LCMV antibodies to prevent the establishment of persistence in both neonatal and adult mice. Suckling BALB/c mouse pups nursed by mothers immunized against LCMV before pregnancy had higher survival rates following infection than controls and withstood challenge doses of up to 400 PFU without becoming persistently infected. To establish that maternal antibody alone and not maternally derived T cells provided this protection, nonimmune mothers were infused with monoclonal anti-LCMV neutralizing antibodies within 24 h after delivering their pups. Pups nursing on these passively immunized mothers were resistant to persistent LCMV infection. The establishment of persistence in adult BALB/c mice by the immunosuppressive, macrophage-tropic LCMV variant, clone 13 was also prevented by prophylactic treatment with anti-LCMV monoclonal antibodies. However, the protection afforded by passively acquired antibody was found to be incomplete if the recipients lacked functional CD8+ T cells. While 65% of neonatal athymic (nu/nu) mice nursed by immune nu/+ dams resisted low-dose viral challenge (25 PFU), the majority of nude pups challenged with high doses of virus (100 PFU) became persistently infected. Also, protection was incomplete in beta2-microglobulin knockout mice, which lack functional CD8+ T cells, suggesting that a cooperative effect was exerted by the combination of neutralizing antibody and endogenous T cells. These results indicate that antibodies provide an effective barrier to the establishment of persistent infections in immunocompetent mice and reaffirm that vaccines which induce strong humoral responses may provide efficient protection against arenavirus infections.

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Selected References

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  1. Ahmed R., Hahn C. S., Somasundaram T., Villarete L., Matloubian M., Strauss J. H. Molecular basis of organ-specific selection of viral variants during chronic infection. J Virol. 1991 Aug;65(8):4242–4247. doi: 10.1128/jvi.65.8.4242-4247.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ahmed R., Salmi A., Butler L. D., Chiller J. M., Oldstone M. B. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J Exp Med. 1984 Aug 1;160(2):521–540. doi: 10.1084/jem.160.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baldridge J. R., Buchmeier M. J. Mechanisms of antibody-mediated protection against lymphocytic choriomeningitis virus infection: mother-to-baby transfer of humoral protection. J Virol. 1992 Jul;66(7):4252–4257. doi: 10.1128/jvi.66.7.4252-4257.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baldridge J. R., Pearce B. D., Parekh B. S., Buchmeier M. J. Teratogenic effects of neonatal arenavirus infection on the developing rat cerebellum are abrogated by passive immunotherapy. Virology. 1993 Dec;197(2):669–677. doi: 10.1006/viro.1993.1642. [DOI] [PubMed] [Google Scholar]
  5. Borrow P., Evans C. F., Oldstone M. B. Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression. J Virol. 1995 Feb;69(2):1059–1070. doi: 10.1128/jvi.69.2.1059-1070.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borrow P., Tishon A., Oldstone M. B. Infection of lymphocytes by a virus that aborts cytotoxic T lymphocyte activity and establishes persistent infection. J Exp Med. 1991 Jul 1;174(1):203–212. doi: 10.1084/jem.174.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buchmeier M. J., Welsh R. M., Dutko F. J., Oldstone M. B. The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv Immunol. 1980;30:275–331. doi: 10.1016/s0065-2776(08)60197-2. [DOI] [PubMed] [Google Scholar]
  8. Doherty P. C., Hou S., Southern P. J. Lymphocytic choriomeningitis virus induces a chronic wasting disease in mice lacking class I major histocompatibility complex glycoproteins. J Neuroimmunol. 1993 Jul;46(1-2):11–17. doi: 10.1016/0165-5728(93)90228-q. [DOI] [PubMed] [Google Scholar]
  9. HOTCHIN J. The biology of lymphocytic choriomeningitis infection: virus-induced immune disease. Cold Spring Harb Symp Quant Biol. 1962;27:479–499. doi: 10.1101/sqb.1962.027.001.046. [DOI] [PubMed] [Google Scholar]
  10. Haywood A. M. Patterns of persistent viral infections. N Engl J Med. 1986 Oct 9;315(15):939–948. doi: 10.1056/NEJM198610093151506. [DOI] [PubMed] [Google Scholar]
  11. King C. C., de Fries R., Kolhekar S. R., Ahmed R. In vivo selection of lymphocyte-tropic and macrophage-tropic variants of lymphocytic choriomeningitis virus during persistent infection. J Virol. 1990 Nov;64(11):5611–5616. doi: 10.1128/jvi.64.11.5611-5616.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
  13. Lehmann-Grube F., Löhler J., Utermöhlen O., Gegin C. Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the beta 2-microglobulin gene. J Virol. 1993 Jan;67(1):332–339. doi: 10.1128/jvi.67.1.332-339.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Matloubian M., Concepcion R. J., Ahmed R. CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J Virol. 1994 Dec;68(12):8056–8063. doi: 10.1128/jvi.68.12.8056-8063.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Matloubian M., Kolhekar S. R., Somasundaram T., Ahmed R. Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus. J Virol. 1993 Dec;67(12):7340–7349. doi: 10.1128/jvi.67.12.7340-7349.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oldstone M. B., Blount P., Southern P. J., Lampert P. W. Cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system. Nature. 1986 May 15;321(6067):239–243. doi: 10.1038/321239a0. [DOI] [PubMed] [Google Scholar]
  17. Oldstone M. B., Dixon F. J. Disease accompanying in utero viral infection. The role of maternal antibody in tissue injury after transplacental infection with lymphocytic choriomeningitis virus. J Exp Med. 1972 Apr 1;135(4):827–838. doi: 10.1084/jem.135.4.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oldstone M. B., Tishon A., Eddleston M., de la Torre J. C., McKee T., Whitton J. L. Vaccination to prevent persistent viral infection. J Virol. 1993 Jul;67(7):4372–4378. doi: 10.1128/jvi.67.7.4372-4378.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Prober C. G., Arvin A. M. Perinatal viral infections. Eur J Clin Microbiol. 1987 Jun;6(3):245–261. doi: 10.1007/BF02017608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scarlatti G., Albert J., Rossi P., Hodara V., Biraghi P., Muggiasca L., Fenyö E. M. Mother-to-child transmission of human immunodeficiency virus type 1: correlation with neutralizing antibodies against primary isolates. J Infect Dis. 1993 Jul;168(1):207–210. doi: 10.1093/infdis/168.1.207. [DOI] [PubMed] [Google Scholar]
  21. Wright K. E., Buchmeier M. J. Antiviral antibodies attenuate T-cell-mediated immunopathology following acute lymphocytic choriomeningitis virus infection. J Virol. 1991 Jun;65(6):3001–3006. doi: 10.1128/jvi.65.6.3001-3006.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wright K. E., Salvato M. S., Buchmeier M. J. Neutralizing epitopes of lymphocytic choriomeningitis virus are conformational and require both glycosylation and disulfide bonds for expression. Virology. 1989 Aug;171(2):417–426. doi: 10.1016/0042-6822(89)90610-7. [DOI] [PubMed] [Google Scholar]

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