Abstract
Recombinant vaccinia virus expressing the Lassa virus (LV) envelope glycoprotein precursor, V-LSGPC, was used to study the basis of LV-induced cross-protective immunity against the closely related arenavirus lymphocytic choriomeningitis virus (LCMV). C3H/HeJ mice primed with V-LSGPC developed neither circulating antibodies nor CD8+ cytotoxic T cells specific for LCMV, yet they resisted a normally lethal LCMV challenge. Spleen cells from such mice gave a proliferative response to LCMV in vitro that was inhibitable by anti-CD4 antibody. Synthetic peptides corresponding to predicted T-cell sites common to the envelope glycoprotein precursor (GP-C) of LV and that of LCMV were used to map the specificity of the proliferative response to an epitope located between amino acids 403 and 417 of LV GP-C. Several CD4+ T-cell clones specific for the 403-417 peptide were isolated and found to produce gamma interferon in response to both the peptide and LCMV. One of these clones, C9, was selected for further study. C9 lysed I-AK-bearing target cells, and when adoptively transferred to C3H/HeJ mice, it was capable of mediating both a peptide-specific delayed hypersensitivity reaction and resistance to lethal LCMV challenge. These collective findings demonstrate, for the first time, that CD4+ T cells can play a major role in arenavirus-specific cross-protective immunity.
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Selected References
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- Ahmed R., Butler L. D., Bhatti L. T4+ T helper cell function in vivo: differential requirement for induction of antiviral cytotoxic T-cell and antibody responses. J Virol. 1988 Jun;62(6):2102–2106. doi: 10.1128/jvi.62.6.2102-2106.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Auperin D. D., Esposito J. J., Lange J. V., Bauer S. P., Knight J., Sasso D. R., McCormick J. B. Construction of a recombinant vaccinia virus expressing the Lassa virus glycoprotein gene and protection of guinea pigs from a lethal Lassa virus infection. Virus Res. 1988 Feb;9(2-3):233–248. doi: 10.1016/0168-1702(88)90033-0. [DOI] [PubMed] [Google Scholar]
- Baenziger J., Hengartner H., Zinkernagel R. M., Cole G. A. Induction or prevention of immunopathological disease by cloned cytotoxic T cell lines specific for lymphocytic choriomeningitis virus. Eur J Immunol. 1986 Apr;16(4):387–393. doi: 10.1002/eji.1830160413. [DOI] [PubMed] [Google Scholar]
- Battegay M., Oehen S., Schulz M., Hengartner H., Zinkernagel R. M. Vaccination with a synthetic peptide modulates lymphocytic choriomeningitis virus-mediated immunopathology. J Virol. 1992 Feb;66(2):1199–1201. doi: 10.1128/jvi.66.2.1199-1201.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Binder D., Kündig T. M. Antiviral protection by CD8+ versus CD4+ T cells. CD8+ T cells correlating with cytotoxic activity in vitro are more efficient in antivaccinia virus protection than CD4-dependent IL. J Immunol. 1991 Jun 15;146(12):4301–4307. [PubMed] [Google Scholar]
- Buchmeier M. J., Parekh B. S. Protein structure and expression among arenaviruses. Curr Top Microbiol Immunol. 1987;133:41–57. doi: 10.1007/978-3-642-71683-6_4. [DOI] [PubMed] [Google Scholar]
- Buckley S. M., Casals J., Downs W. G. Isolation and antigenic characterization of Lassa virus. Nature. 1970 Jul 11;227(5254):174–174. doi: 10.1038/227174a0. [DOI] [PubMed] [Google Scholar]
- Cherwinski H. M., Schumacher J. H., Brown K. D., Mosmann T. R. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. doi: 10.1084/jem.166.5.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cole G. A., Nathanson N. Lymphocytic choriomeningitis. Pathogenesis. Prog Med Virol. 1974;18(0):94–110. [PubMed] [Google Scholar]
- Curry R. C., Kiener P. A., Spitalny G. L. A sensitive immunochemical assay for biologically active MuIFN-gamma. J Immunol Methods. 1987 Nov 23;104(1-2):137–142. doi: 10.1016/0022-1759(87)90497-2. [DOI] [PubMed] [Google Scholar]
- Eichelberger M., Allan W., Zijlstra M., Jaenisch R., Doherty P. C. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med. 1991 Oct 1;174(4):875–880. doi: 10.1084/jem.174.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fisher-Hoch S. P., McCormick J. B., Auperin D., Brown B. G., Castor M., Perez G., Ruo S., Conaty A., Brammer L., Bauer S. Protection of rhesus monkeys from fatal Lassa fever by vaccination with a recombinant vaccinia virus containing the Lassa virus glycoprotein gene. Proc Natl Acad Sci U S A. 1989 Jan;86(1):317–321. doi: 10.1073/pnas.86.1.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frame J. D., Baldwin J. M., Jr, Gocke D. J., Troup J. M. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings. Am J Trop Med Hyg. 1970 Jul;19(4):670–676. doi: 10.4269/ajtmh.1970.19.670. [DOI] [PubMed] [Google Scholar]
- Fung-Leung W. P., Kündig T. M., Zinkernagel R. M., Mak T. W. Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression. J Exp Med. 1991 Dec 1;174(6):1425–1429. doi: 10.1084/jem.174.6.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilden D. H., Cole G. A., Monjan A. A., Nathanson N. Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. I. Cyclophosphamide-mediated induction by the virus-carrier state in adult mice. J Exp Med. 1972 Apr 1;135(4):860–873. doi: 10.1084/jem.135.4.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glimcher L. H., McKean D. J., Choi E., Seidman J. G. Complex regulation of class II gene expression: analysis with class II mutant cell lines. J Immunol. 1985 Nov;135(5):3542–3550. [PubMed] [Google Scholar]
- Goronzy J., Weyand C. M., Fathman C. G. Long-term humoral unresponsiveness in vivo, induced by treatment with monoclonal antibody against L3T4. J Exp Med. 1986 Sep 1;164(3):911–925. doi: 10.1084/jem.164.3.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hany M., Oehen S., Schulz M., Hengartner H., Mackett M., Bishop D. H., Overton H., Zinkernagel R. M. Anti-viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia-recombinant virus expressing LCMV-WE nucleoprotein or glycoprotein. Eur J Immunol. 1989 Mar;19(3):417–424. doi: 10.1002/eji.1830190302. [DOI] [PubMed] [Google Scholar]
- Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- JOKLIK W. K. The purification fo four strains of poxvirus. Virology. 1962 Sep;18:9–18. doi: 10.1016/0042-6822(62)90172-1. [DOI] [PubMed] [Google Scholar]
- Johnson E. D., Cole G. A. Functional heterogeneity of lymphocytic choriomeningitis virus-specfic T lymphocytes. I. Identification of effector amd memory subsets. J Exp Med. 1975 Apr 1;141(4):866–881. [PMC free article] [PubMed] [Google Scholar]
- Joly E., Salvato M., Whitton J. L., Oldstone M. B. Polymorphism of cytotoxic T-lymphocyte clones that recognize a defined nine-amino-acid immunodominant domain of lymphocytic choriomeningitis virus glycoprotein. J Virol. 1989 May;63(5):1845–1851. doi: 10.1128/jvi.63.5.1845-1851.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jonjić S., Pavić I., Lucin P., Rukavina D., Koszinowski U. H. Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes. J Virol. 1990 Nov;64(11):5457–5464. doi: 10.1128/jvi.64.11.5457-5464.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiley M. P., Lange J. V., Johnson K. M. Protection of rhesus monkeys from Lassa virus by immunisation with closely related Arenavirus. Lancet. 1979 Oct 6;2(8145):738–738. doi: 10.1016/s0140-6736(79)90659-7. [DOI] [PubMed] [Google Scholar]
- Leist T. P., Cobbold S. P., Waldmann H., Aguet M., Zinkernagel R. M. Functional analysis of T lymphocyte subsets in antiviral host defense. J Immunol. 1987 Apr 1;138(7):2278–2281. [PubMed] [Google Scholar]
- Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
- Monjan A. A., Cole G. A., Gilden D. H., Nathanson N. Pathogenesis of cerebellar hypoplasia produced by lymphocytic choriomeningitis virus infection of neonatal rats. 1. Evolution of disease following infection at 4 days of age. J Neuropathol Exp Neurol. 1973 Jan;32(1):110–124. doi: 10.1097/00005072-197301000-00007. [DOI] [PubMed] [Google Scholar]
- Moskophidis D., Cobbold S. P., Waldmann H., Lehmann-Grube F. Mechanism of recovery from acute virus infection: treatment of lymphocytic choriomeningitis virus-infected mice with monoclonal antibodies reveals that Lyt-2+ T lymphocytes mediate clearance of virus and regulate the antiviral antibody response. J Virol. 1987 Jun;61(6):1867–1874. doi: 10.1128/jvi.61.6.1867-1874.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moskophidis D., Fang L., Gossmann J., Lehmann-Grube F. Mechanism of recovery from acute virus infection. IX. Clearance of lymphocytic choriomeningitis (LCM) virus from the feet of mice undergoing LCM virus-specific delayed-type hypersensitivity reaction. J Gen Virol. 1989 Dec;70(Pt 12):3305–3316. doi: 10.1099/0022-1317-70-12-3305. [DOI] [PubMed] [Google Scholar]
- Muller D., Koller B. H., Whitton J. L., LaPan K. E., Brigman K. K., Frelinger J. A. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Science. 1992 Mar 20;255(5051):1576–1578. doi: 10.1126/science.1347959. [DOI] [PubMed] [Google Scholar]
- Nabavi N., Ghogawala Z., Myer A., Griffith I. J., Wade W. F., Chen Z. Z., McKean D. J., Glimcher L. H. Antigen presentation abrogated in cells expressing truncated Ia molecules. J Immunol. 1989 Mar 1;142(5):1444–1447. [PubMed] [Google Scholar]
- Nickell S. P., Freeman R. R., Cole G. A. Depression of virus-specific cytotoxic T-cell responses during murine malaria. Parasite Immunol. 1987 Mar;9(2):161–174. doi: 10.1111/j.1365-3024.1987.tb00497.x. [DOI] [PubMed] [Google Scholar]
- Peters C. J., Jahrling P. B., Liu C. T., Kenyon R. H., McKee K. T., Jr, Barrera Oro J. G. Experimental studies of arenaviral hemorrhagic fevers. Curr Top Microbiol Immunol. 1987;134:5–68. doi: 10.1007/978-3-642-71726-0_2. [DOI] [PubMed] [Google Scholar]
- Rothbard J. B., Taylor W. R. A sequence pattern common to T cell epitopes. EMBO J. 1988 Jan;7(1):93–100. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern P. J., Bishop D. H. Sequence comparison among arenaviruses. Curr Top Microbiol Immunol. 1987;133:19–39. doi: 10.1007/978-3-642-71683-6_3. [DOI] [PubMed] [Google Scholar]
- Spitalny G. L., Havell E. A. Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. J Exp Med. 1984 May 1;159(5):1560–1565. doi: 10.1084/jem.159.5.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanley C. J., Johannsson A., Self C. H. Enzyme amplification can enhance both the speed and the sensitivity of immunoassays. J Immunol Methods. 1985 Oct 24;83(1):89–95. doi: 10.1016/0022-1759(85)90061-4. [DOI] [PubMed] [Google Scholar]
- Stohlman S. A., Matsushima G. K., Casteel N., Weiner L. P. In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection but do not inhibit virus replication. J Immunol. 1986 Apr 15;136(8):3052–3056. [PubMed] [Google Scholar]
- Thomsen A. R., Marker O. MHC and non-MHC genes regulate elimination of lymphocytic choriomeningitis virus and antiviral cytotoxic T lymphocyte and delayed-type hypersensitivity mediating T lymphocyte activity in parallel. J Immunol. 1989 Feb 15;142(4):1333–1341. [PubMed] [Google Scholar]
- Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
- Williamson J. S., Stohlman S. A. Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells. J Virol. 1990 Sep;64(9):4589–4592. doi: 10.1128/jvi.64.9.4589-4592.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson S. M., Clegg J. C. Sequence analysis of the S RNA of the African arenavirus Mopeia: an unusual secondary structure feature in the intergenic region. Virology. 1991 Feb;180(2):543–552. doi: 10.1016/0042-6822(91)90068-m. [DOI] [PubMed] [Google Scholar]
