In vivo imaging of murid herpesvirus-4 infection.

Animal Structures/virology; Animals; Female; Genes, Reporter; Herpesviridae Infections/pathology/virology; Luciferases/genetics/metabolism; Mice; Mice, Inbred BALB C; Rhadinovirus/growth & development; Tumor Virus Infections/pathology/virology; Whole Body Imaging

Abstract :

[en] Luciferase-based imaging allows a global view of microbial pathogenesis. We applied this technique to gammaherpesvirus infection by inserting a luciferase expression cassette into the genome of murine herpesvirus-4 (MuHV-4). The recombinant virus strongly expressed luciferase in lytically infected cells without significant attenuation. We used it to compare different routes of virus inoculation. After intranasal infection of anaesthetized mice, luciferase was expressed in the nose and lungs for 7-10 days and in lymphoid tissue, most consistently the superficial cervical lymph nodes, for up to 30 days. Gastrointestinal infection was not observed. Intraperitoneal infection was very different to intranasal, with strong luciferase expression in the liver, kidneys, intestines, reproductive tract and spleen, but none in the nose or lungs. The nose has not previously been identified as a site of MuHV-4 infection. After intranasal infection of non-anaesthetized mice, it was the only site of non-lymphoid luciferase expression. Nevertheless, lymphoid colonization and persistence were still established, even at low inoculation doses. In contrast, virus delivered orally was very poorly infectious. Inoculation route therefore had a major impact on pathogenesis. Low dose intranasal infection without anaesthesia seems most likely to mimic natural transmission, and may therefore be particularly informative about normal viral gene functions.

Disciplines :

Microbiology

Author, co-author :

Milho, Ricardo

Smith, Christopher M

Marques, Sofia

Alenquer, Marta

May, Janet S

Gillet, Laurent ; Université de Liège - ULiège > Immunologie et vaccinologie

Gaspar, Miguel

Efstathiou, Stacey

Simas, J Pedro

Stevenson, Philip G

Language :

English

Title :

In vivo imaging of murid herpesvirus-4 infection.

Publication date :

2009

Journal title :

Journal of General Virology

ISSN :

0022-1317

eISSN :

1465-2099

Publisher :

Society for General Microbiology, London, United Kingdom

Volume :

Issue :

Pt 1

Pages :

21-32

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 20 November 2010

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Bibliography

Adler, H., Messerle, M., Wagner, M. & Koszinowski, U. H. (2000). Cloning and mutagenesis of the munne gammaherpesvirus 68 genome as an infectious bacterial artificial chromosome. J Virol 74, 6964-6974.
Adler, H., Messerle, M. & Koszinowski, U. H. (2001). Virus reconstituted from infectious bacterial artificial chromosome (BAC)-doned murine gammaherpesvirus 68 acquires wild-type properties in vivo only after excision of BAC vector sequences. J Virol 75, 5692-5696.
Beiz, G. T., Wilson, N. S., Kupresanin, F., Mount A. M. & Smith, C. M. (2007). Shaping naive and memory CD8 + T cell responses in pathogen infections through antigen presentation. Adv Exp Med Biol 590, 31-42.
Bennett, N. J., May, J. S. & Stevenson, P. G. (2005). Gamma-herpesvirus latency requires T cell evasion during episome maintenance. PLoS Biol 3, e120.
Blasdell, K, McCracken, C., Morris, A, Nash, A. A., Begion, M., Bennett, M. & Stewart, J. P. (2003). The wood mouse is a natural host for murid herpesvirus 4. J Gen Virol 84, 111-113.
Blaskovic, D., Stancekova, M., Svobodova, J. & Mistrikova, J. (1980). Isolation of five strains of herpesviruses from two species of free living small rodents. Acta Virol 24, 468.
Blaskovic, D., Stancekova, D. & Rajcani, J. (1984). Experimental pathogenesis of marine herpesvirus in newborn mice. Acta Virol 28, 225-231.
Boname, J. M. & Stevenson, P. G. (2001). MHC class I ubiquitination by a viral PHD/LAP finger protein. Immunity 15, 627-636.
Boname, J. M., de Lima, B. D., Lehner, P. J. & Stevenson, P. G. (2004). Viral degradation of the MHC class I peptide loading complex. Immunity 20, 305-317.
Bridgeman, A., Stevenson, P. G., Simas, J. P. & Efstathiou, S. (2001). A secreted chemokine binding protein encoded by marine gamma-herpesvirus-68 is necessary for the establishment of a normal latent load. J Exp Med 194, 301-312.
Chastel, C., Beaucournu, J. P., Chastel, O., Legrand, M. C. & Le Goff, F. (1994). A herpesvirus from an European shrew (Crocidura russula). Acta Virol 38, 309.
Coleman, H. M., de Lima, B., Morton, V. & Stevenson, P. G. (2003). Marine gammaherpesvirus 68 lacking thymidine kinase shows severe attenuation of lytic cycle replication in vivo but still establishes latency. J Virol 77, 2410-2417.
de Lima, B. D., May, J. S. & Stevenson, P. G. (2004). Marine gammaherpesvirus 68 lacking gp150 shows defective virion release but establishes normal latency in vivo. J Virol 78, 5103-5112.
de Lima, B. D., May, J. S., Marques, S., Simas, J. P. & Stevenson, P. G. (2005). Marine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. J Gen Virol 86, 31-40.
Flano, E., Kim, I. J., Woodland, D. L. & Blackman, M. A. (2002). γ-herpesvirus latency is preferentially maintained in splenic germinal center and memory B cells. J Exp Med 196, 1363-1372.
Gangappa, S., van Dyk, L F., Jewett, T. J., Speck S. H. & Virgin, H. W. (2002). Identification of the in vivo role of a viral bcl-2. J Exp Med 195, 931-940.
Gaspar, M., Gill, M. B, Loesing, J. B., May, J. S. & Stevenson, P. G. (2008). Multiple functions for ORF75c in murid herpesvirus-4 infection. PLoS One 3, e2781.
Gillet, L., Adler, H. & Stevenson, P. G. (2007a). Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection. PLoS One 2, e347.
Gillet, L., May, J. S. & Stevenson, P. G. (2007b). Post-exposure vaccination improves gammaherpesvirus neutralization. PLoS One 2, e899.
Gillet L., Coleco, S. & Stevenson, P. G. ((2008). The murid herpesvirus-4 gH/gL binds to glycosaminoglycans. PLoS ONE 3, e1669.
Hayashi, K., Hayashi, M., Jalkanen, M., Firestone, J. H., Trelstad, R. L. & Bernfield, M. (1987). Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study. J Histochem Cytochem 35, 1079-1088.
Hutchens, M. & Luker, G. D. (2007). Applications of bioluminescence imaging to the study of infectious diseases. Cell Microbiol 9, 2315-2322.
Kapadia, S. B., Molina, H., van Eierkel, V., Speck S. H. & Virgin, H. W. (1999). Murine gammaherpesvirus 68 encodes a functional regulator of complement activation. J Virol 73, 7658-7670.
Kozuch, O., Reichel, M., Lesso, J., Remenová, A., Labuda, M., Lysy, J. & Mistríková J. (1993). Further isolation of marine herpesviruses from small mammals in southwestern Slovakia. Acta Virol 37, 101-105.
Laichalk, L. L., Hochberg, D., Babcock, G. J., Freeman, R. B. & Thorley-Lawson, D. A. (2002). The dispersal of mucosal memory B cells: evidence from persistent EBV infection. Immunity 16, 745-754.
Liu, L., Flaño, E., Usherwood, E. J., Surman, S., Blackman, M. A. & Woodland, D. L. (1999). Lytic cycle T cell epitopes are expressed in two distinct phases during MHV-68 infection. J Immunol 163, 868-874.
Lybarger, L., Wang, X., Harris, M. R., Virgin, H. W. & Hansen, T. H. (2003). Virus subversion of the MHC class I peptide-loading complex. Immunity 18, 121-130.
Marques, S., Efstathiou, S., Smith, K. G., Haury, M. & Simas, J. P. (2003). Selective gene expression of latent murine gammaherpesvirus 68 in B lymphocytes. J Virol 77, 7308-7318.
May, J. S., Coleman, H. M., Smillie, B., Efstathiou, S. & Stevenson, P. G. (2004). Forced lytic replication impairs host colonization by a latency-deficient mutant of murine gammaherpesvirus-68. J Gen Virol 85, 137-146.
May, J. S., Coleman, H. M., Boname, J. M. & Stevenson, P. G. (2005a). The murine gammaherpesvirus-68 ORF28 encodes a non-essential virion glycoprotein. J Gen Virol 86, 919-928.
May, J. S., de Lima, B. D., Colaco, S. & Stevenson, P. G. (2005b). Intercellular gamma-herpesvirus dissemination involves co-ordinated intracellular membrane protein transport. Traffic 6, 780-793.
Mistrikova, J., Kozuch, O., Klempa, B., Kontsekova, E., Labuda, M. & Mrmusova, M. (2000). New findings on the ecology and epidemiology of murine herpes virus isolated in Slovakia. Bratisl Lek Listy 101, 157-162 (in Slovak).
Nash, A. A. & Sunil-Chandra, N. P. (1994). Interactions of the murine gammaherpesvirus with the immune system. Curr Opin Immunol 6, 560-563.
Nash, A. A., Dutia, B. M., Stewart, J. P. & Davison, A. J. (2001). Natural history of murine γ-herpesvirus infection. Philos Trans R Soc Lond B Biol Sci 356, 569-579.
Parry, C. M., Simas, J. P., Smith, V. P., Stewart, C. A., Minson, A. C., Efstathiou, S. & Alcami, A. (2000). A broad spectrum secreted chemokine binding protein encoded by a herpesvirus. J ExpMed 191, 573-578.
Peacock, J. W. & Bost, K. L. (2000). Infection of intestinal epithelial cells and development of systemic disease following gastric instillation of murine gammaherpesvirus-68. J Gen Virol 81, 421-429.
Persons, D. A., Mehaffey, M. G., Kaleko, M., Nienhuis, A. W. & Vanin, E. F. (1998). An improved method for generating retroviral producer clones for vectors lacking a selectable marker gene. Blood Cells Mol Dis 24, 167-182.
Raslova, H., Berebbi,M., Rajcani, J., Sarasin, A.,Matis, J. & Kudelova, M. (2001). Susceptibility of mouse mammary glands to murine gammaherpesvirus 72 (MHV-72) infection: evidence of MHV-72 transmission via breast milk. Microb Pathog 31, 47-58.
Rice, J., de Lima, B., Stevenson, F. K. & Stevenson, P. G. (2002). A γ-herpesvirus immune evasion gene allows tumor cells in vivo to escape attack by cytotoxic T cells specific for a tumor epitope. Eur J Immunol 32, 3481-3487.
Rosa, G. T., Gillet, L., Smith, C. M., de Lima, B. D. & Stevenson, P. G. (2007). IgG Fc receptors provide an alternative infection route for murine gamma-herpesvirus-68. PLoS One 2, e560.
Simas, J. P., Swann, D., Bowden, R. & Efstathiou, S. (1999). Analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection. J Gen Virol 80, 75-82.
Smith, C. M., Rosa, G. T., May, J. S., Bennett, N. J., Mount, A. M., Belz, G. T. & Stevenson, P. G. (2006). CD4+ T cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo. Eur J Immunol 36, 3186-3197.
Smith, C. M., Gill, M. B., May, J. S. & Stevenson, P. G. (2007). Murine gammaherpesvirus-68 inhibits antigen presentation by dendritic cells. PLoS One 2, e1048.
Song, M. J., Hwang, S., Wong, W. H., Wu, T. T., Lee, S., Liao, H. I. & Sun, R. (2005). Identification of viral genes essential for replication of murine γ-herpesvirus 68 using signature-tagged mutagenesis. Proc Natl Acad Sci U S A 102, 3805-3810.
Speck, S. H. & Virgin, H. W. (1999). Host and viral genetics of chronic infection: a mouse model of gamma-herpesvirus pathogenesis. Curr Opin Microbiol 2, 403-409.
Stevenson, P. G. (2004). Immune evasion by gamma-herpesviruses. Curr Opin Immunol 16, 456-462.
Stevenson, P. G. & Doherty, P. C. (1998). Kinetic analysis of the host immune response to a murine gammaherpesvirus. J Virol 72, 943-949.
Stevenson, P. G. & Efstathiou, S. (2005). Immune mechanisms in murine gammaherpesvirus-68 infection. Viral Immunol 18, 445-456.
Stevenson, P. G., Belz, G. T., Altman, J. D. & Doherty, P. C. (1999a). Changing patterns of dominance in the CD8+ T cell response during acute and persistent murine c-herpesvirus infection. Eur J Immunol 29, 1059-1067.
Stevenson, P. G., Cardin, R. D., Christensen, J. P. & Doherty, P. C. (1999b). Immunological control of a murine gammaherpesvirus independent of CD8+ T cells. J Gen Virol 80, 477-483.
Stevenson, P.G., Belz,G. T., Castrucci, M.R., Altman, J.D. & Doherty, P.C. (1999c). A γ-herpesvirus sneaks through a CD8+ T cell response primed to a lytic-phase epitope. Proc Natl Acad Sci U S A 96, 9281-9286.
Stevenson, P. G., Boname, J. M., de Lima, B. & Efstathiou, S. (2002a). A battle for survival: immune control and immune evasion in murine γ-herpesvirus-68 infection. Microbes Infect 4, 1177-1182.
Stevenson, P. G., May, J. S., Smith, X. G., Marques, S., Adler, H., Koszinowski, U. H., Simas, J. P. & Efstathiou, S. (2002b). K3-mediated evasion of CD8+ T cells aids amplification of a latent γ-herpesvirus. Nat Immunol 3, 733-740.
Sunil-Chandra, N. P., Efstathiou, S., Arno, J. & Nash, A. A. (1992). Virological and pathological features of mice infected with murine gammaherpesvirus 68. J Gen Virol 73, 2347-2356.
Terry, L. A., Stewart, J. P., Nash, A. A. & Fazakerley, J. K. (2000). Murine gammaherpesvirus-68 infection of and persistence in the central nervous system. J Gen Virol 81, 2635-2643.
Thorley-Lawson, D. A. (2001). Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1, 75-82.
Tibbetts, S. A., Loh, J., Van Berkel, V., McClellan, J. S., Jacoby, M. A., Kapadia, S. B., Speck, S. H. & Virgin, H. W. (2003). Establishment and maintenance of gammaherpesvirus latency are independent of infective dose and route of infection. J Virol 77, 7696-7701.
van Berkel, V., Preiter, K., Virgin, H. W. & Speck, S. H. (1999). Identification and initial characterization of the murine gammaherpesvirus 68 gene M3, encoding an abundantly secreted protein. J Virol 73, 4524-4529.
van Berkel, V., Barrett, J., Tiffany, H. L., Fremont, D. H., Murphy, P. M., McFadden, G., Speck, S. H. & Virgin, H. W. (2000). Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action. J Virol 74, 6741-6747.
Weck, K. E., Barkon, M. L., Yoo, L. I., Speck, S. H. & Virgin, H. W. (1996). Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68. J Virol 70, 6775-6780.
Yao, Q. Y., Rickinson, A. B. & Epstein, M. A. (1985). A re-examination of the Epstein-Barr virus carrier state in healthy seropositive individuals. Int J Cancer 35, 35-42.
Yin, Y., Manoury, B. & Fahraeus, R. (2003). Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1. Science 301, 1371-1374.