Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Apr;142(4):1061–1071.

Human foamy virus proteins accumulate in neurons and induce multinucleated giant cells in the brain of transgenic mice.

A Aguzzi 1, E F Wagner 1, K O Netzer 1, K Bothe 1, I Anhauser 1, A Rethwilm 1
PMCID: PMC1886887  PMID: 8386440

Abstract

Human foamy virus (HFV) is a retrovirus encoding structural genes and, like human immunodeficiency virus and human T cell leukemia virus I, several ancillary reading frames collectively termed the be1 genes. We have previously shown that HFV transgenic mice develop an encephalopathy with neuronal loss in hippocampus and cerebral cortex. We have now raised and characterized rabbit antisera to various recombinant portions of gag, pol, env, and bel-1, the viral trans-activator. Immunoreactivity for gag and bel-1 was observed in nuclei and processes of hippocampal and cortical neurons before the onset of morphological lesions and correlated with the appearance of HFV mRNA. Astrocyte-derived multinucleated giant cells containing HFV proteins were present in the brain of transgenic mice coexpressing full-length HFV genes but not in mice expressing truncated gag and env, suggesting that these genes contain a fusogenic domain. Expression of full-length structural genes decreased the life expectancy of transgenic mice, implying an adjuvant role for these proteins in HFV-induced brain damage.

Full text

PDF
1061

Images in this article

1064Figure 2
on p.1064
1066Figure 3
on p.1066
1067Figure 4
on p.1067
1068Figure 5
on p.1068

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Achong B. G., Mansell P. W., Epstein M. A., Clifford P. An unusual virus in cultures from a human nasopharyngeal carcinoma. J Natl Cancer Inst. 1971 Feb;46(2):299–307. [PubMed] [Google Scholar]
  2. Aguzzi A., Bothe K., Anhauser I., Horak I., Rethwilm A., Wagner E. F. Expression of human foamy virus is differentially regulated during development in transgenic mice. New Biol. 1992 Mar;4(3):225–237. [PubMed] [Google Scholar]
  3. Aguzzi A., Bothe K., Wagner E. F., Rethwilm A., Horak I. Human foamy virus: an underestimated neuropathogen? Brain Pathol. 1992 Jan;2(1):61–69. [PubMed] [Google Scholar]
  4. Aguzzi A., Kleihues P., Heckl K., Wiestler O. D. Cell type-specific tumor induction in neural transplants by retrovirus-mediated oncogene transfer. Oncogene. 1991 Jan;6(1):113–118. [PubMed] [Google Scholar]
  5. Aguzzi A., Wagner E. F., Williams R. L., Courtneidge S. A. Sympathetic hyperplasia and neuroblastomas in transgenic mice expressing polyoma middle T antigen. New Biol. 1990 Jun;2(6):533–543. [PubMed] [Google Scholar]
  6. Bothe K., Aguzzi A., Lassmann H., Rethwilm A., Horak I. Progressive encephalopathy and myopathy in transgenic mice expressing human foamy virus genes. Science. 1991 Aug 2;253(5019):555–557. doi: 10.1126/science.1650034. [DOI] [PubMed] [Google Scholar]
  7. Ellinger S., Glockshuber R., Jahn G., Plückthun A. Cleavage of procaryotically expressed human immunodeficiency virus fusion proteins by factor Xa and application in western blot (immunoblot) assays. J Clin Microbiol. 1989 May;27(5):971–976. doi: 10.1128/jcm.27.5.971-976.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Flügel R. M., Rethwilm A., Maurer B., Darai G. Nucleotide sequence analysis of the env gene and its flanking regions of the human spumaretrovirus reveals two novel genes. EMBO J. 1987 Jul;6(7):2077–2084. doi: 10.1002/j.1460-2075.1987.tb02473.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Loh P. C., Matsuura F., Mizumoto C. Seroepidemiology of human syncytial virus: antibody prevalence in the Pacific. Intervirology. 1980;13(2):87–90. doi: 10.1159/000149112. [DOI] [PubMed] [Google Scholar]
  10. Mahnke C., Kashaiya P., Rössler J., Bannert H., Levin A., Blattner W. A., Dietrich M., Luande J., Löchelt M., Friedman-Kien A. E. Human spumavirus antibodies in sera from African patients. Arch Virol. 1992;123(3-4):243–253. doi: 10.1007/BF01317261. [DOI] [PubMed] [Google Scholar]
  11. Maurer B., Serfling E., ter Meulen V., Rethwilm A. Transcription factor AP-1 modulates the activity of the human foamy virus long terminal repeat. J Virol. 1991 Nov;65(11):6353–6357. doi: 10.1128/jvi.65.11.6353-6357.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Muller H. K., Ball G., Epstein M. A., Achong B. G., Lenoir G., Levin A. The prevalence of naturally occurring antibodies to human syncytial virus in East African populations. J Gen Virol. 1980 Apr;47(2):399–406. doi: 10.1099/0022-1317-47-2-399. [DOI] [PubMed] [Google Scholar]
  13. Muranyi W., Flügel R. M. Analysis of splicing patterns of human spumaretrovirus by polymerase chain reaction reveals complex RNA structures. J Virol. 1991 Feb;65(2):727–735. doi: 10.1128/jvi.65.2.727-735.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Netzer K. O., Rethwilm A., Maurer B., ter Meulen V. Identification of the major immunogenic structural proteins of human foamy virus. J Gen Virol. 1990 May;71(Pt 5):1237–1241. doi: 10.1099/0022-1317-71-5-1237. [DOI] [PubMed] [Google Scholar]
  15. Rethwilm A., Baunach G., Netzer K. O., Maurer B., Borisch B., ter Meulen V. Infectious DNA of the human spumaretrovirus. Nucleic Acids Res. 1990 Feb 25;18(4):733–738. doi: 10.1093/nar/18.4.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rethwilm A., Darai G., Rösen A., Maurer B., Flügel R. M. Molecular cloning of the genome of human spumaretrovirus. Gene. 1987;59(1):19–28. doi: 10.1016/0378-1119(87)90262-9. [DOI] [PubMed] [Google Scholar]
  17. Rethwilm A., Erlwein O., Baunach G., Maurer B., ter Meulen V. The transcriptional transactivator of human foamy virus maps to the bel 1 genomic region. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):941–945. doi: 10.1073/pnas.88.3.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rethwilm A., Mori K., Maurer B., ter Meulen V. Transacting transcriptional activation of human spumaretrovirus LTR in infected cells. Virology. 1990 Apr;175(2):568–571. doi: 10.1016/0042-6822(90)90442-t. [DOI] [PubMed] [Google Scholar]
  19. Wagner E. F. EMBO medal review. On transferring genes into stem cells and mice. EMBO J. 1990 Oct;9(10):3024–3032. doi: 10.1002/j.1460-2075.1990.tb07498.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Werner J., Gelderblom H. Isolation of foamy virus from patients with de Quervain thyroiditis. Lancet. 1979 Aug 4;2(8136):258–259. doi: 10.1016/s0140-6736(79)90275-7. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES