1887

Abstract

We used the murine gammaherpesvirus 68 (HV-68), which serves as a model for human gammaherpesvirus infection, to determine whether age at infection altered the pattern of gammaherpesvirus pathogenesis. We infected mice intranasally at 8 days old (pups) and 6 weeks old (adults) to investigate differences in HV-68 pathogenesis. There was no difference between adults or pups in acute infection in the lungs at 6 days post-infection (p.i.). However, mice infected as pups exhibited a more disseminated viral infection with viral DNA detected in the spleen, liver and heart as measured by quantitative PCR (Q-PCR). In addition, viral DNA was detected in the lungs of mice infected as pups until 60 days p.i. Three viral transcripts (M2, M3 and M9) were expressed at both 30 and 60 days p.i. In contrast, no viral DNA or mRNA expression was detected in lungs of mice infected as adults at 30 or 60 days p.i. Mice infected as adults experienced a peak in latent infection in the spleen at 16 days p.i., corresponding with an increase in splenic weight and expansion of the V4 CD8 T-cell population, similar to infectious mononucleosis observed following infection of young adults with Epstein–Barr virus. However, the increase in splenic weight of infected pups was not as pronounced and no significant increase in V4 CD8 T-cell expansion was observed in infected pups. Together, these data suggest that the pathogenesis of murine gammaherpesvirus HV-68 is age-dependent.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83470-0
2008-05-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/5/1114.html?itemId=/content/journal/jgv/10.1099/vir.0.83470-0&mimeType=html&fmt=ahah

References

  1. Adkins B., Hamilton K. 1992; Freshly isolated, murine neonatal T cells produce IL-4 in response to anti-CD3 stimulation. J Immunol 149:3448–3455
    [Google Scholar]
  2. Adkins B., Ghanei A., Hamilton K. 1993; Developmental regulation of IL-4, IL-2, and IFN-gamma production by murine peripheral T lymphocytes. J Immunol 151:6617–6626
    [Google Scholar]
  3. Biggar R. J., Henle G., Bocker J., Lennette E. T., Fleisher G., Henle W. 1978; Primary Epstein–Barr virus infections in African infants. II. Clinical and serological observations during seroconversion. Int J Cancer 22:244–250 [CrossRef]
    [Google Scholar]
  4. Callan M. F. 2003; The evolution of antigen-specific CD8+ T cell responses after natural primary infection of humans with Epstein-Barr virus. Viral Immunol 16:3–16 [CrossRef]
    [Google Scholar]
  5. Cardin R. D., Brooks J. W., Sarawar S. R., Doherty P. C. 1996; Progressive loss of CD8+ T cell-mediated control of a γ -herpesvirus in the absence of CD4+ T cells. J Exp Med 184:863–871 [CrossRef]
    [Google Scholar]
  6. Chomczynski P., Sacchi N. 1987; Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162:156–159
    [Google Scholar]
  7. Cote P. J., Korba B. E., Miller R. H., Jacob J. R., Baldwin B. H., Hornbuckle W. E., Purcell R. H., Tennant B. C., Gerin J. L. 2000; Effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection. Hepatology 31:190–200 [CrossRef]
    [Google Scholar]
  8. de-The G. 1977; Is Burkitt's lymphoma related to perinatal infection by Epstein–Barr virus?. Lancet 1:335–338
    [Google Scholar]
  9. Ehtisham S., Sunil-Chandra N. P., Nash A. A. 1993; Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells. J Virol 67:5247–5252
    [Google Scholar]
  10. 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 [CrossRef]
    [Google Scholar]
  11. Flano E., Kim I. J., Moore J., Woodland D. L., Blackman M. A. 2003; Differential γ -herpesvirus distribution in distinct anatomical locations and cell subsets during persistent infection in mice. J Immunol 170:3828–3834 [CrossRef]
    [Google Scholar]
  12. Garvy B. A. 2003; Host defense against pulmonary infection in neonates. Clin Appl Immunol Rev 4:205–223
    [Google Scholar]
  13. Garvy B. A., Qureshi M. H. 2000; Delayed inflammatory response to Pneumocystis carinii infection in neonatal mice is due to an inadequate lung environment. J Immunol 165:6480–6486 [CrossRef]
    [Google Scholar]
  14. Goriely S., Van Lint C., Dadkhah R., Libin M., De Wit D., Demonte D., Willems F., Goldman M. 2004; A defect in nucleosome remodeling prevents IL-12 ( p35 ) gene transcription in neonatal dendritic cells. J Exp Med 199:1011–1016 [CrossRef]
    [Google Scholar]
  15. Hausler M., Sellhaus B., Scheithauer S., Gaida B., Kuropka S., Siepmann K., Panek A., Berg W., Teubner A. other authors 2007; Myocarditis in newborn wild-type BALB/c mice infected with the murine gamma herpesvirus MHV-68. Cardiovasc Res 76:323–330 [CrossRef]
    [Google Scholar]
  16. Hobbs M. V., Weigle W. O., Noonan D. J., Torbett B. E., McEvilly R. J., Koch R. J., Cardenas G. J., Ernst D. N. 1993; Patterns of cytokine gene expression by CD4+ T cells from young and old mice. J Immunol 150:3602–3614
    [Google Scholar]
  17. Imperial J. C. 1999; Natural history of chronic hepatitis B and C. J Gastroenterol Hepatol 14:Suppl.S1–S5 [CrossRef]
    [Google Scholar]
  18. 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 [CrossRef]
    [Google Scholar]
  19. Mbulaiteye S. M., Pfeiffer R. M., Engels E. A., Marshall V., Bakaki P. M., Owor A. M., Ndugwa C. M., Katongole-Mbidde E., Goedert J. J. other authors 2004; Detection of Kaposi sarcoma-associated herpesvirus DNA in saliva and buffy-coat samples from children with sickle cell disease in Uganda. J Infect Dis 190:1382–1386 [CrossRef]
    [Google Scholar]
  20. Menne S., Roneker C. A., Roggendorf M., Gerin J. L., Cote P. J., Tennant B. C. 2002; Deficiencies in the acute-phase cell-mediated immune response to viral antigens are associated with development of chronic woodchuck hepatitis virus infection following neonatal inoculation. J Virol 76:1769–1780 [CrossRef]
    [Google Scholar]
  21. Moormann A. M., Chelimo K., Sumba O. P., Lutzke M. L., Ploutz-Snyder R., Newton D., Kazura J., Rochford R. 2005; Exposure to holoendemic malaria results in elevated Epstein–Barr virus loads in children. J Infect Dis 191:1233–1238 [CrossRef]
    [Google Scholar]
  22. Nakamura I., Nupp J. T., Cowlen M., Hall W. C., Tennant B. C., Casey J. L., Gerin J. L., Cote P. J. 2001; Pathogenesis of experimental neonatal woodchuck hepatitis virus infection: chronicity as an outcome of infection is associated with a diminished acute hepatitis that is temporally deficient for the expression of interferon gamma and tumor necrosis factor-alpha messenger RNAs. Hepatology 33:439–447 [CrossRef]
    [Google Scholar]
  23. Piedimonte G. 2002; Origins of reactive airways disease in early life: do viral infections play a role?. Acta Paediatr Suppl 91:6–11
    [Google Scholar]
  24. Pullan C. R., Hey E. N. 1982; Wheezing, asthma, and pulmonary dysfunction 10 years after infection with respiratory syncytial virus in infancy. Br Med J (Clin Res Ed) 284, 1665–1669 [CrossRef]
    [Google Scholar]
  25. Rajcani J., Blaskovic D., Svobodova J., Ciampor F., Huckova D., Stanekova D. 1985; Pathogenesis of acute and persistent murine herpesvirus infection in mice. Acta Virol 29:51–60
    [Google Scholar]
  26. Rickinson A. B., Kieff E. 2001; Epstein–Barr virus. In Fields Virology , 4th edn. pp 2575–2627Edited by Knipe D. M., Howley. Philadelphia, PA: Lippincott, Williams & Wilkins;
    [Google Scholar]
  27. Rochford R., Lutzke M. L., Alfinito R. S., Clavo A., Cardin R. D. 2001; Kinetics of murine gammaherpesvirus 68 gene expression following infection of murine cells in culture and in mice. J Virol 75:4955–4963 [CrossRef]
    [Google Scholar]
  28. Schuetze N., Schoeneberger S., Mueller U., Freudenberg M. A., Alber G., Straubinger R. K. 2005; IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella enteritidis and the impact of IL-10 in bone marrow-derived macrophages. Int Immunol 17:649–659 [CrossRef]
    [Google Scholar]
  29. Sunil-Chandra N. P., Efstathiou S., Arno J., Nash A. A. 1992a; Virological and pathological features of mice infected with murine gamma-herpesvirus 68. J Gen Virol 73:2347–2356 [CrossRef]
    [Google Scholar]
  30. Sunil-Chandra N. P., Efstathiou S., Nash A. A. 1992b; Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo . J Gen Virol 73:3275–3279 [CrossRef]
    [Google Scholar]
  31. Tibbetts S. A., Loh J., Van Berkel V., McClellan J. S., Jacoby M. A., Kapadia S. B., Speck S. H., Virgin H. W. IV 2003; Establishment and maintenance of gammaherpesvirus latency are independent of infective dose and route of infection. J Virol 77:7696–7701 [CrossRef]
    [Google Scholar]
  32. Tripp R. A., Hamilton-Easton A. M., Cardin R. D., Nguyen P., Behm F. G., Woodland D. L., Doherty P. C., Blackman M. A. 1997; Pathogenesis of an infectious mononucleosis-like disease induced by a murine γ -herpesvirus: role for a viral superantigen?. J Exp Med 185:1641–1650 [CrossRef]
    [Google Scholar]
  33. Tu W., Chen S., Sharp M., Dekker C., Manganello A. M., Tongson E. C., Maecker H. T., Holmes T. H., Wang Z. other authors 2004; Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in immunocompetent young children. J Immunol 172:3260–3267 [CrossRef]
    [Google Scholar]
  34. Usherwood E. J., Ross A. J., Allen D. J., Nash A. A. 1996; Murine gammaherpesvirus-induced splenomegaly: a critical role for CD4 T cells. J Gen Virol 77:627–630 [CrossRef]
    [Google Scholar]
  35. van Dyk L. F., Virgin H. W. IV, Speck S. H. 2000; The murine gammaherpesvirus 68 v–cyclin is a critical regulator of reactivation from latency. J Virol 74:7451–7461 [CrossRef]
    [Google Scholar]
  36. Wang Y., Menne S., Jacob J. R., Tennant B. C., Gerin J. L., Cote P. J. 2003; Role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection. Hepatology 37:771–780 [CrossRef]
    [Google Scholar]
  37. Weck K. E., Barkon M. L., Yoo L. I., Speck S. H., Virgin H. I. 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
    [Google Scholar]
  38. Weinberg J. B., Lutzke M. L., Alfinito R., Rochford R. 2004; Mouse strain differences in the chemokine response to acute lung infection with a murine gammaherpesvirus. Viral Immunol 17:69–77 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83470-0
Loading
/content/journal/jgv/10.1099/vir.0.83470-0
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