Skip to main content

Advertisement

SpringerLink
Log in

Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus

  • Published:
Archives of Virology Aims and scope Submit manuscript

Summary.

Murine cytomegalovirus (MCMV) immediate-early (IE) 2 protein has been reported to be dispensable for growth and latency in mice. Therefore, its role in viral pathogenesis and tissue tropism is not known. Here we prepared specific antibodies to the IE2 and IE3 proteins by using fusion proteins expressed in Escherichia coli as antigens. Immunostaining of MCMV-infected cultured fibroblasts revealed IE2 protein to be expressed diffusely in the nucleoplasm similar to the IE1 protein. In contrast, expression of the IE3 protein, 88 kDa, exhibited a punctate pattern in the nucleus in the early phase of infection then diminished. In the brain of neonatal mice infected with MCMV, both IE2 and IE3 proteins were detected immunohistochemically in the cells of the ventricular walls early in infection. When the infection was prolonged, the IE2 protein was expressed in neurons of the cortex and hippocampus, while the IE3 protein was preferentially expressed in glial cells in the early phase of infection, and its levels declined during the infection. These results suggest that the IE2 protein may play a role in persistent infection in neurons, whereas the IE3 protein, expressed preferentially in glial cells, may play the main role in acute infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • J-H Ahn W-J Jang GS Hayward (1999) ArticleTitleThe human cytomegalovirus IE2 and UL112-113 proteins accumulate in viral DNA replication compartments that initiate from the periphery of promyelocytic leukemia protein-associated nuclear bodies (PODs or ND10) J Virol 73 10458–10471 Occurrence Handle10559364 Occurrence Handle1:CAS:528:DyaK1MXnsV2ls7w%3D

    PubMed  CAS  Google Scholar 

  • S Aiba-Masago S Baba R-Y Li Y Shinmura I Kosugi Y Arai M Nishimura Y Tsutsui (1999) ArticleTitleMurine cytomegalovirus immediate-early promoter directs astrocyte-specific expression in transgenic mice Am J Pathol 154 735–743 Occurrence Handle10079251 Occurrence Handle1:STN:280:DyaK1M7otVOlsg%3D%3D

    PubMed  CAS  Google Scholar 

  • A Angulo P Ghazal M Messerle (2000) ArticleTitleThe major immediate-early gene ie3 of mouse cytomegalovirus is essential for virual growth J Virol 74 11129–11136 Occurrence Handle11070009 Occurrence Handle1:CAS:528:DC%2BD3MXitFWmtb8%3D Occurrence Handle10.1128/JVI.74.23.11129-11136.2000

    Article  PubMed  CAS  Google Scholar 

  • Y Arai M Ishiwata S Baba H Kawasaki I Kosugi R-Y Li T Tsuchida K Miura Y Tsutsui (2003) ArticleTitleNeuron-specific activation of murine cytomegalovirus early gene e1 promoter in transgenic mice Am J Pathol 163 643–652 Occurrence Handle12875983 Occurrence Handle1:CAS:528:DC%2BD3sXmslSnsbw%3D

    PubMed  CAS  Google Scholar 

  • W Cao MBA Oldstone JC de la Torre (1997) ArticleTitleViral persistent infection affects both transcriptional and posttranscriptional regulation of neuron-specific molecule GAP43 Virology 230 147–154 Occurrence Handle9143270 Occurrence Handle1:CAS:528:DyaK2sXivVGku74%3D Occurrence Handle10.1006/viro.1997.8458

    Article  PubMed  CAS  Google Scholar 

  • RD Cardin GB Abenes CA Stoddart ES Mocarski (1995) ArticleTitleNurine cytomegalovirus IE2, an activator of gene expression, is dispensable for growth and latency in mice Virology 209 236–241 Occurrence Handle7747475 Occurrence Handle1:CAS:528:DyaK2MXls12qtrw%3D Occurrence Handle10.1006/viro.1995.1249

    Article  PubMed  CAS  Google Scholar 

  • P Cinque R Marenzi D Ceresa (1997) ArticleTitleCytomegalovirus infections of the nervous system Intervirology 40 85–97 Occurrence Handle9450226 Occurrence Handle1:STN:280:DyaK1c7htFyqtA%3D%3D Occurrence Handle10.1159/000150536

    Article  PubMed  CAS  Google Scholar 

  • GJ Demmler (1991) ArticleTitleInfectious diseases society of America and centers for disease control. Summary of a workshop on surveillance for congenital cytomegalovirus disease Rev Infect Dis 13 315–329 Occurrence Handle1645882 Occurrence Handle1:STN:280:DyaK3M3lt1Krsg%3D%3D

    PubMed  CAS  Google Scholar 

  • UA Gompels J Nicholas G Lawrence M Jones BJ Thomson MED Martin S Eftstathiou M Craxton HA Macaulay (1995) ArticleTitleThe DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution Virology 209 29–51 Occurrence Handle7747482 Occurrence Handle1:CAS:528:DyaK2MXls12qsL8%3D Occurrence Handle10.1006/viro.1995.1228

    Article  PubMed  CAS  Google Scholar 

  • GM Keil MR Fibi UH Koszinowski (1984) ArticleTitleTemporal regulation of murine cytomegalovirus transcription and mapping of viral RNA synthesized at immediate early times after infection J Virol 50 784–795 Occurrence Handle6328008 Occurrence Handle1:CAS:528:DyaL2cXks1Kru70%3D

    PubMed  CAS  Google Scholar 

  • GM Keil MR Fibi UH Koszinowski (1985) ArticleTitleCharacterization of the major immediate-early polypeptides encoded by murine cytomegalovirus J Virol 54 422–428 Occurrence Handle2985805 Occurrence Handle1:CAS:528:DyaL2MXitVSrtr8%3D

    PubMed  CAS  Google Scholar 

  • GM Keil A Ebeling-Keil UH Koszinowski (1987) ArticleTitleImmediate-early gene of murine cytomegalovirus: location, transcripts, and transcription products J Virol 61 526–533 Occurrence Handle3027381 Occurrence Handle1:CAS:528:DyaL2sXhtFCgu74%3D

    PubMed  CAS  Google Scholar 

  • I Kosugi H Kawasaki Y Arai Y Tsutsui (2002) ArticleTitleInnate immune responses to cytomegalovirus infection in the developing mouse brain and their evasion by virus-infected neuron Am J Pathol 161 919–928 Occurrence Handle12213720 Occurrence Handle1:CAS:528:DC%2BD38XnsFOisrw%3D

    PubMed  CAS  Google Scholar 

  • A Krmpotic I Bubic B Polic P Lucin S Jonjic (2003) ArticleTitlePathogenesis of murine cytomegalovirus infection Microbes Infect 5 1265–1277 Occurrence Handle10.1016/j.micinf.2003.09.007 Occurrence Handle1:CAS:528:DC%2BD3sXovVelt7s%3D

    Article  CAS  Google Scholar 

  • RY Li Y Tsutsui (2000) ArticleTitleGrowth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus Teratology 62 79–85 Occurrence Handle10931504 Occurrence Handle1:CAS:528:DC%2BD3cXlslejsb8%3D Occurrence Handle10.1002/1096-9926(200008)62:2<79::AID-TERA3>3.0.CO;2-S

    Article  PubMed  CAS  Google Scholar 

  • WC Manning ES Mocarski (1988) ArticleTitleInsertional mutagenesis of the nurine cytomegalovirus genome: one prominent α-gene (ie2) is dispensable for growth Virology 167 477–484 Occurrence Handle2849236 Occurrence Handle1:CAS:528:DyaL1MXovFGmsA%3D%3D

    PubMed  CAS  Google Scholar 

  • M Messerle G Keil UH Koszinowski (1991) ArticleTitleStructure and expression of murine cytomegalovirus immediate-early gene 2 J Virol 65 1638–1643 Occurrence Handle1847480 Occurrence Handle1:CAS:528:DyaK3MXkvVKhu7Y%3D

    PubMed  CAS  Google Scholar 

  • M Messerle B Buhler GM Keil UH Koszinowski (1992) ArticleTitleStructural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3 J Virol 66 27–36 Occurrence Handle1309246 Occurrence Handle1:CAS:528:DyaK3sXnsVGhsw%3D%3D

    PubMed  CAS  Google Scholar 

  • ES Mocarski (1996) Cytomegalovirus and their replication BN Fiels DN Knipe PM Howley (Eds) Virology EditionNumber3 Lippincott-Raven Philadelphia 2447–2492

    Google Scholar 

  • ES Mocarski GW Kemble (1996) ArticleTitleRecombinant cytomegaloviruses for study of replication and pathogenesis Intervirology 39 320–330 Occurrence Handle9130042

    PubMed  Google Scholar 

  • Y Nishiyama (2004) ArticleTitleHerpes simplex virus gene products: the accessories reflect her lifestyle well Rev Med Virol 14 33–46 Occurrence Handle14716690 Occurrence Handle1:CAS:528:DC%2BD2cXhs1Gltbw%3D Occurrence Handle10.1002/rmv.409

    Article  PubMed  CAS  Google Scholar 

  • WD Rawlinson HE Farrell BG Barrell (1996) ArticleTitleAnalysis of the complete DNA sequence of murine cytomegalovirus J Virol 70 8833–8894 Occurrence Handle8971012 Occurrence Handle1:CAS:528:DyaK28XmvVGqsLw%3D

    PubMed  CAS  Google Scholar 

  • MJ Reddehase J Podlech NKA Grzimek (2002) ArticleTitleMouse models of cytomegalovirus latency: overview J Clin Virol 25 s23–s36 Occurrence Handle12361754 Occurrence Handle1:CAS:528:DC%2BD38XnsVagtL0%3D Occurrence Handle10.1016/S1386-6532(02)00087-2

    Article  PubMed  CAS  Google Scholar 

  • AH Sharpe BN Fields (1985) ArticleTitlePathogenesis of viral infections. Basic concepts derived from the reovirus model N Engl J Med 312 486–497 Occurrence Handle2982096 Occurrence Handle1:CAS:528:DyaL2MXhs1Cmu7o%3D Occurrence Handle10.1056/NEJM198502213120806

    Article  PubMed  CAS  Google Scholar 

  • Y Shinmura S Aiba-Masago I Kosugi RY Li S Baba Y Tsutsui (1997) ArticleTitleDifferential expression of the immediate-early and early antigens in neuronal and glial cells of developing mouse brains infected with murine cytomegalovirus Am J Pathol 151 1331–1340 Occurrence Handle9358759 Occurrence Handle1:CAS:528:DyaK2sXntlOksbc%3D

    PubMed  CAS  Google Scholar 

  • M Shulman CD Wilde G Kohler (1978) ArticleTitleA better cell line for making hybridomas secreting specific antibodies Nature 276 269–270 Occurrence Handle714156 Occurrence Handle1:STN:280:DyaE1M%2Fltlalug%3D%3D Occurrence Handle10.1038/276269a0

    Article  PubMed  CAS  Google Scholar 

  • DB Smith KS Johnson (1988) ArticleTitleSingle-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase Gene 67 31–40 Occurrence Handle3047011 Occurrence Handle1:CAS:528:DyaL1cXlt1Ghs7g%3D Occurrence Handle10.1016/0378-1119(88)90005-4

    Article  PubMed  CAS  Google Scholar 

  • S Stagno RF Pass G Cloud WJ Bright RE Henderson PD Walton DA Veren F Page (1986) ArticleTitleAlford CA: Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome JAMA 256 1904–1908 Occurrence Handle3020264 Occurrence Handle1:STN:280:DyaL2s%2FhtFyqsw%3D%3D Occurrence Handle10.1001/jama.256.14.1904

    Article  PubMed  CAS  Google Scholar 

  • Y Tomooka H Kitani N Jing M Matsushima T Sakakura (1993) ArticleTitleReconstruction of neural tube-like structure in vitro from primary neural precursor cells Proc Natl Acad Sci USA 90 9683–9687 Occurrence Handle8415762 Occurrence Handle1:CAS:528:DyaK3sXms1OgtL0%3D Occurrence Handle10.1073/pnas.90.20.9683

    Article  PubMed  CAS  Google Scholar 

  • H Towbin T Staehelin J Gordon (1979) ArticleTitleElectrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications Proc Natl Acad Sci USA 76 4350–4354 Occurrence Handle388439 Occurrence Handle1:CAS:528:DyaE1MXmtVKltLw%3D Occurrence Handle10.1073/pnas.76.9.4350

    Article  PubMed  CAS  Google Scholar 

  • Y Tsutsui I Naruse (1987) ArticleTitleMurine cytomegalovirus infection of cultured mouse embryos Am J Pathol 127 262–270 Occurrence Handle3034066 Occurrence Handle1:STN:280:DyaL2s3htVGitw%3D%3D

    PubMed  CAS  Google Scholar 

  • Y Tsutsui A Kashiwai N Kawamura S Aiba-Masago I Kosugi (1995) ArticleTitleProlonged infection of mouse brain neurons with murine cytomegalovirus after pre- and perinatal infection Arch Virol 140 1725–1736 Occurrence Handle7503674 Occurrence Handle1:CAS:528:DyaK2MXpvVOkt74%3D Occurrence Handle10.1007/BF01384337

    Article  PubMed  CAS  Google Scholar 

  • Y Tsutsui H Kawasaki I Kosugi (2002) ArticleTitleReactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice culture J Virol 76 7247–7254 Occurrence Handle12072524 Occurrence Handle1:CAS:528:DC%2BD38XltVyls7c%3D Occurrence Handle10.1128/JVI.76.14.7247-7254.2002

    Article  PubMed  CAS  Google Scholar 

  • Y Tsutsui I Kosugi H Kawasaki (2005) ArticleTitleNeuropathogensis in cytomegalovirus infection: indication of the mechanisms using mouse models Rev Med Virol 15 327–345 Occurrence Handle16100703 Occurrence Handle1:CAS:528:DC%2BD2MXhtFaktrfI Occurrence Handle10.1002/rmv.475

    Article  PubMed  CAS  Google Scholar 

  • AN van den Pol ES Mocarski N Saederup J Vieira TJ Meier (1999) ArticleTitleCytomegalovirus cell tropism, replication, and gene transfer in brain J Neurosci 19 10948–10965 Occurrence Handle10594076 Occurrence Handle1:CAS:528:DyaK1MXotVyjtr8%3D

    PubMed  CAS  Google Scholar 

  • TH Weller (1971) ArticleTitleThe cytomegalovirus: ubiquitous agents with protean clinical manifestations N Engl J Med 285 203–214 Occurrence Handle4325893 Occurrence Handle1:STN:280:DyaE3M3hsFertg%3D%3D Occurrence Handle10.1056/NEJM197107222850406

    Article  PubMed  CAS  Google Scholar 

  • H Yamada Y-M Jiang S Oshima T Daikoku Y Yamashita T Tsurumi Y Nishiyama (1998) ArticleTitleCharacterization of the UL55 gene product of herpes simplex virus type 1 J Gen Virol 79 1989–1995 Occurrence Handle9714248 Occurrence Handle1:CAS:528:DyaK1cXlt1Cjs7Y%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    M. Ishiwata, S. Baba, M. Kawashima, I. Kosugi, H. Kawasaki, M. Kaneta, T. Tsuchida & Y. Tsutsui

  2. Department of Obstetrics and Gynecology, Tokyo University Graduate School of Medicine, Tokyo, Japan

    M. Ishiwata & S. Kozuma

Authors
  1. M. Ishiwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Kawashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. Kosugi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Kawasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Kaneta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Tsuchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Kozuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y. Tsutsui
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishiwata, M., Baba, S., Kawashima, M. et al. Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus. Arch Virol 151, 2181–2196 (2006). https://doi.org/10.1007/s00705-006-0793-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-006-0793-0

Keywords

Search

Navigation