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. 1997 Oct;71(10):7337–7344. doi: 10.1128/jvi.71.10.7337-7344.1997

Coinfection of human foreskin fragments with multiple human papillomavirus types (HPV-11, -40, and -LVX82/MM7) produces regionally separate HPV infections within the same athymic mouse xenograft.

N D Christensen 1, W A Koltun 1, N M Cladel 1, L R Budgeon 1, C A Reed 1, J W Kreider 1, P A Welsh 1, S D Patrick 1, H Yang 1
PMCID: PMC192078  PMID: 9311811

Abstract

The athymic mouse xenograft system was used to prepare infectious stocks of two additional anogenital tissue-targeting human papillomaviruses (HPVs) in a manner similar to that for the development of infectious stocks of HPV-11. An anal condyloma from a transplant patient was used as material for extraction of infectious virus, and human foreskin fragments were incubated with the virus suspension and transplanted subrenally into athymic mice. Partial viral sequencing indicated that two rare HPV types (HPV-40 and HPVLVX82/MM7) were concurrently present in both the patient condyloma and the foreskin xenografts, and passage of both types was achieved as a mixed infection with HPV-40 predominating. Xenografts that developed from simultaneous infection of human foreskin fragments with HPV-11, -40, and -LVX82/MM7 virions produced regionally separate areas of HPV-11 and -40 infection as determined by in situ hybridization. In addition, in situ hybridization with HPV-40 and HPVLVX82/MM7 DNA probes demonstrated that both of these HPV types were present as adjacent but separate infections within the same anal condyloma of the transplant patient. These studies indicate that multiple HPV types can simultaneously infect genital tissue and that each HPV type predominantly maintains regional separation within the same papilloma.

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Selected References

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  1. Bauer H. M., Ting Y., Greer C. E., Chambers J. C., Tashiro C. J., Chimera J., Reingold A., Manos M. M. Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA. 1991 Jan 23;265(4):472–477. [PubMed] [Google Scholar]
  2. Bergeron C., Ferenczy A., Shah K. V., Naghashfar Z. Multicentric human papillomavirus infections of the female genital tract: correlation of viral types with abnormal mitotic figures, colposcopic presentation, and location. Obstet Gynecol. 1987 May;69(5):736–742. [PubMed] [Google Scholar]
  3. Bernard H. U., Chan S. Y., Manos M. M., Ong C. K., Villa L. L., Delius H., Peyton C. L., Bauer H. M., Wheeler C. M. Identification and assessment of known and novel human papillomaviruses by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence, and phylogenetic algorithms. J Infect Dis. 1994 Nov;170(5):1077–1085. doi: 10.1093/infdis/170.5.1077. [DOI] [PubMed] [Google Scholar]
  4. Bonnez W., Rose R. C., Da Rin C., Borkhuis C., de Mesy Jensen K. L., Reichman R. C. Propagation of human papillomavirus type 11 in human xenografts using the severe combined immunodeficiency (SCID) mouse and comparison to the nude mouse model. Virology. 1993 Nov;197(1):455–458. doi: 10.1006/viro.1993.1611. [DOI] [PubMed] [Google Scholar]
  5. Brandsma J. L., Brownstein D. G., Xiao W., Longley B. J. Papilloma formation in human foreskin xenografts after inoculation of human papillomavirus type 16 DNA. J Virol. 1995 Apr;69(4):2716–2721. doi: 10.1128/jvi.69.4.2716-2721.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown D. R., Bryan J. T., Cramer H., Katz B. P., Handy V., Fife K. H. Detection of multiple human papillomavirus types in condylomata acuminata from immunosuppressed patients. J Infect Dis. 1994 Oct;170(4):759–765. doi: 10.1093/infdis/170.4.759. [DOI] [PubMed] [Google Scholar]
  7. Christensen N. D., Cladel N. M., Reed C. A., Budgeon L. R., Welsh P. A., Patrick S. D., Kreider J. W. Laboratory production of infectious stocks of rabbit oral papillomavirus. J Gen Virol. 1996 Aug;77(Pt 8):1793–1798. doi: 10.1099/0022-1317-77-8-1793. [DOI] [PubMed] [Google Scholar]
  8. Christensen N. D., Höpfl R., DiAngelo S. L., Cladel N. M., Patrick S. D., Welsh P. A., Budgeon L. R., Reed C. A., Kreider J. W. Assembled baculovirus-expressed human papillomavirus type 11 L1 capsid protein virus-like particles are recognized by neutralizing monoclonal antibodies and induce high titres of neutralizing antibodies. J Gen Virol. 1994 Sep;75(Pt 9):2271–2276. doi: 10.1099/0022-1317-75-9-2271. [DOI] [PubMed] [Google Scholar]
  9. Christensen N. D., Kreider J. W. Antibody-mediated neutralization in vivo of infectious papillomaviruses. J Virol. 1990 Jul;64(7):3151–3156. doi: 10.1128/jvi.64.7.3151-3156.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crum C. P., Mitao M., Levine R. U., Silverstein S. Cervical papillomaviruses segregate within morphologically distinct precancerous lesions. J Virol. 1985 Jun;54(3):675–681. doi: 10.1128/jvi.54.3.675-681.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Delius H., Hofmann B. Primer-directed sequencing of human papillomavirus types. Curr Top Microbiol Immunol. 1994;186:13–31. doi: 10.1007/978-3-642-78487-3_2. [DOI] [PubMed] [Google Scholar]
  12. Dollard S. C., Wilson J. L., Demeter L. M., Bonnez W., Reichman R. C., Broker T. R., Chow L. T. Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. OFF. Genes Dev. 1992 Jul;6(7):1131–1142. doi: 10.1101/gad.6.7.1131. [DOI] [PubMed] [Google Scholar]
  13. Evander M., Frazer I. H., Payne E., Qi Y. M., Hengst K., McMillan N. A. Identification of the alpha6 integrin as a candidate receptor for papillomaviruses. J Virol. 1997 Mar;71(3):2449–2456. doi: 10.1128/jvi.71.3.2449-2456.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Firzlaff J. M., Kiviat N. B., Beckmann A. M., Jenison S. A., Galloway D. A. Detection of human papillomavirus capsid antigens in various squamous epithelial lesions using antibodies directed against the L1 and L2 open reading frames. Virology. 1988 Jun;164(2):467–477. doi: 10.1016/0042-6822(88)90561-2. [DOI] [PubMed] [Google Scholar]
  15. Gaukroger J., Bradley A., O'Neil B., Smith K., Campo S., Jarrett W. Induction of virus-producing tumours in athymic nude mice by bovine papillomavirus type 4. Vet Rec. 1989 Oct 7;125(15):391–392. doi: 10.1136/vr.125.15.391. [DOI] [PubMed] [Google Scholar]
  16. Ghim S., Christensen N. D., Kreider J. W., Jenson A. B. Comparison of neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts. Int J Cancer. 1991 Sep 9;49(2):285–289. doi: 10.1002/ijc.2910490224. [DOI] [PubMed] [Google Scholar]
  17. Heino P., Skyldberg B., Lehtinen M., Rantala I., Hagmar B., Kreider J. W., Kirnbauer R., Dillner J. Human papillomavirus type 16 capsids expose multiple type-restricted and type-common antigenic epitopes. J Gen Virol. 1995 May;76(Pt 5):1141–1153. doi: 10.1099/0022-1317-76-5-1141. [DOI] [PubMed] [Google Scholar]
  18. Hildesheim A., Schiffman M. H., Gravitt P. E., Glass A. G., Greer C. E., Zhang T., Scott D. R., Rush B. B., Lawler P., Sherman M. E. Persistence of type-specific human papillomavirus infection among cytologically normal women. J Infect Dis. 1994 Feb;169(2):235–240. doi: 10.1093/infdis/169.2.235. [DOI] [PubMed] [Google Scholar]
  19. Jarrett W. F., O'Neil B. W., Gaukroger J. M., Smith K. T., Laird H. M., Campo M. S. Studies on vaccination against papillomaviruses: the immunity after infection and vaccination with bovine papillomaviruses of different types. Vet Rec. 1990 May 12;126(19):473–475. [PubMed] [Google Scholar]
  20. Jenson A. B., Lancaster W. D., Hartmann D. P., Shaffer E. L., Jr Frequency and distribution of papillomavirus structural antigens in verrucae, multiple papillomas, and condylomata of the oral cavity. Am J Pathol. 1982 May;107(2):212–218. [PMC free article] [PubMed] [Google Scholar]
  21. Kreider J. W., Bartlett G. L. The Shope papilloma-carcinoma complex of rabbits: a model system of neoplastic progression and spontaneous regression. Adv Cancer Res. 1981;35:81–110. doi: 10.1016/s0065-230x(08)60909-4. [DOI] [PubMed] [Google Scholar]
  22. Kreider J. W., Howett M. K., Leure-Dupree A. E., Zaino R. J., Weber J. A. Laboratory production in vivo of infectious human papillomavirus type 11. J Virol. 1987 Feb;61(2):590–593. doi: 10.1128/jvi.61.2.590-593.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kreider J. W., Howett M. K., Wolfe S. A., Bartlett G. L., Zaino R. J., Sedlacek T., Mortel R. Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata. Nature. 1985 Oct 17;317(6038):639–641. doi: 10.1038/317639a0. [DOI] [PubMed] [Google Scholar]
  24. Kreider J. W., Patrick S. D., Cladel N. M., Welsh P. A. Experimental infection with human papillomavirus type 1 of human hand and foot skin. Virology. 1990 Jul;177(1):415–417. doi: 10.1016/0042-6822(90)90503-j. [DOI] [PubMed] [Google Scholar]
  25. Kurman R. J., Shah K. H., Lancaster W. D., Jenson A. B. Immunoperoxidase localization of papillomavirus antigens in cervical dysplasia and vulvar condylomas. Am J Obstet Gynecol. 1981 Aug 15;140(8):931–935. doi: 10.1016/0002-9378(81)90087-9. [DOI] [PubMed] [Google Scholar]
  26. Lauricella-Lefebvre M. A., Piette J., Lifrange E., Lambotte R., Gerard P., Rentier B. High rate of multiple genital HPV infections detected by DNA hybridization. J Med Virol. 1992 Apr;36(4):265–270. doi: 10.1002/jmv.1890360406. [DOI] [PubMed] [Google Scholar]
  27. Lorincz A. T., Reid R., Jenson A. B., Greenberg M. D., Lancaster W., Kurman R. J. Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. Obstet Gynecol. 1992 Mar;79(3):328–337. doi: 10.1097/00006250-199203000-00002. [DOI] [PubMed] [Google Scholar]
  28. Majewski S., Breitburd F., Skopinska M., Croissant O., Jablonska S., Orth G. A mouse model for studying epidermodysplasia-verruciformis-associated carcinogenesis. Int J Cancer. 1994 Mar 1;56(5):727–730. doi: 10.1002/ijc.2910560519. [DOI] [PubMed] [Google Scholar]
  29. Manos M. M., Waldman J., Zhang T. Y., Greer C. E., Eichinger G., Schiffman M. H., Wheeler C. M. Epidemiology and partial nucleotide sequence of four novel genital human papillomaviruses. J Infect Dis. 1994 Nov;170(5):1096–1099. doi: 10.1093/infdis/170.5.1096. [DOI] [PubMed] [Google Scholar]
  30. Meyers C., Frattini M. G., Hudson J. B., Laimins L. A. Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation. Science. 1992 Aug 14;257(5072):971–973. doi: 10.1126/science.1323879. [DOI] [PubMed] [Google Scholar]
  31. Müller M., Gissmann L., Cristiano R. J., Sun X. Y., Frazer I. H., Jenson A. B., Alonso A., Zentgraf H., Zhou J. Papillomavirus capsid binding and uptake by cells from different tissues and species. J Virol. 1995 Feb;69(2):948–954. doi: 10.1128/jvi.69.2.948-954.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ong C. K., Bernard H. U., Villa L. L. Identification of genomic sequences of three novel human papillomavirus sequences in cervical smears of Amazonian Indians. J Infect Dis. 1994 Nov;170(5):1086–1088. doi: 10.1093/infdis/170.5.1086. [DOI] [PubMed] [Google Scholar]
  33. Poljak M., Seme K. Rapid detection and typing of human papillomaviruses by consensus polymerase chain reaction and enzyme-linked immunosorbent assay. J Virol Methods. 1996 Feb;56(2):231–238. doi: 10.1016/0166-0934(95)01969-3. [DOI] [PubMed] [Google Scholar]
  34. Roden R. B., Greenstone H. L., Kirnbauer R., Booy F. P., Jessie J., Lowy D. R., Schiller J. T. In vitro generation and type-specific neutralization of a human papillomavirus type 16 virion pseudotype. J Virol. 1996 Sep;70(9):5875–5883. doi: 10.1128/jvi.70.9.5875-5883.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Roden R. B., Kirnbauer R., Jenson A. B., Lowy D. R., Schiller J. T. Interaction of papillomaviruses with the cell surface. J Virol. 1994 Nov;68(11):7260–7266. doi: 10.1128/jvi.68.11.7260-7266.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Soler C., Chardonnet Y., Allibert P., Euvrard S., Mandrand B., Thivolet J. Detection of multiple types of human papillomavirus in a giant condyloma from a grafted patient. Analysis by immunohistochemistry, in situ hybridisation, Southern blot and polymerase chain reaction. Virus Res. 1992 May;23(3):193–208. doi: 10.1016/0168-1702(92)90108-l. [DOI] [PubMed] [Google Scholar]
  37. Sterling J., Stanley M., Gatward G., Minson T. Production of human papillomavirus type 16 virions in a keratinocyte cell line. J Virol. 1990 Dec;64(12):6305–6307. doi: 10.1128/jvi.64.12.6305-6307.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zhou J., Stenzel D. J., Sun X. Y., Frazer I. H. Synthesis and assembly of infectious bovine papillomavirus particles in vitro. J Gen Virol. 1993 Apr;74(Pt 4):763–768. doi: 10.1099/0022-1317-74-4-763. [DOI] [PubMed] [Google Scholar]
  39. de Villiers E. M., Hirsch-Behnam A., von Knebel-Doeberitz C., Neumann C., zur Hausen H. Two newly identified human papillomavirus types (HPV 40 and 57) isolated from mucosal lesions. Virology. 1989 Jul;171(1):248–253. doi: 10.1016/0042-6822(89)90532-1. [DOI] [PubMed] [Google Scholar]

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