Skip to main content
PMC home page
Emerging Infectious Diseases logoLink to Emerging Infectious Diseases
. 1996 Jul-Sep;2(3):159–167. doi: 10.3201/eid0203.960301

Molecular approaches to the identification of unculturable infectious agents.

S J Gao 1, P S Moore 1
PMCID: PMC2626790  PMID: 8903225

Abstract

New molecular biologic techniques, particularly representational difference analysis, consensus sequence-based polymerase chain reaction, and complementary DNA library screening, have led to the identification of several previously unculturable infectious agents. New agents have been found in tissues from patients with Kaposi's sarcoma, non-A, non-B hepatitis, hantavirus pulmonary syndrome, bacillary angiomatosis, and Whipple's disease by using these techniques without direct culture. The new methods rely on identifying subgenomic fragments from the suspected agent. After a unique nucleic acid fragment belonging to an agent is isolated from diseased tissues, the fragment can be sequenced and used as a probe to identify additional infected tissues or obtain extended portions of the agent's genome. For agents that cannot be cultured by standard techniques, these approaches have proved invaluable for identification and characterization studies. Applying these techniques to other human diseases of suspected infectious etiology may rapidly elucidate novel candidate pathogens.

Full Text

The Full Text of this article is available as a PDF (334.5 KB).

Selected References

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

  1. Adams V., Kempf W., Schmid M., Müller B., Briner J., Burg G. Absence of herpesvirus-like DNA sequences in skin cancers of non-immunosuppressed patients. Lancet. 1995 Dec 23;346(8991-8992):1715–1716. doi: 10.1016/s0140-6736(95)92887-1. [DOI] [PubMed] [Google Scholar]
  2. Alter H. J. The cloning and clinical implications of HGV and HGBV-C. N Engl J Med. 1996 Jun 6;334(23):1536–1537. doi: 10.1056/NEJM199606063342310. [DOI] [PubMed] [Google Scholar]
  3. Ambroziak J. A., Blackbourn D. J., Herndier B. G., Glogau R. G., Gullett J. H., McDonald A. R., Lennette E. T., Levy J. A. Herpes-like sequences in HIV-infected and uninfected Kaposi's sarcoma patients. Science. 1995 Apr 28;268(5210):582–583. doi: 10.1126/science.7725108. [DOI] [PubMed] [Google Scholar]
  4. Angritt P., Tuur S. M., Macher A. M., Smith K. J., Park C. S., Hobin F. P., Myrie-Williams C. Epithelioid angiomatosis in HIV infection: neoplasm or cat-scratch disease? Lancet. 1988 Apr 30;1(8592):996–996. doi: 10.1016/s0140-6736(88)91813-2. [DOI] [PubMed] [Google Scholar]
  5. Archibald C. P., Schechter M. T., Craib K. J., Le T. N., Douglas B., Willoughby B., O'Shaughnessy M. Risk factors for Kaposi's sarcoma in the Vancouver Lymphadenopathy-AIDS Study. J Acquir Immune Defic Syndr. 1990;3 (Suppl 1):S18–S23. [PubMed] [Google Scholar]
  6. Archibald C. P., Schechter M. T., Le T. N., Craib K. J., Montaner J. S., O'Shaughnessy M. V. Evidence for a sexually transmitted cofactor for AIDS-related Kaposi's sarcoma in a cohort of homosexual men. Epidemiology. 1992 May;3(3):203–209. doi: 10.1097/00001648-199205000-00004. [DOI] [PubMed] [Google Scholar]
  7. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  8. Beral V., Bull D., Darby S., Weller I., Carne C., Beecham M., Jaffe H. Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS. Lancet. 1992 Mar 14;339(8794):632–635. doi: 10.1016/0140-6736(92)90793-3. [DOI] [PubMed] [Google Scholar]
  9. Beral V., Bull D., Jaffe H., Evans B., Gill N., Tillett H., Swerdlow A. J. Is risk of Kaposi's sarcoma in AIDS patients in Britain increased if sexual partners came from United States or Africa? BMJ. 1991 Mar 16;302(6777):624–625. doi: 10.1136/bmj.302.6777.624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Beral V., Peterman T. A., Berkelman R. L., Jaffe H. W. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection? Lancet. 1990 Jan 20;335(8682):123–128. doi: 10.1016/0140-6736(90)90001-l. [DOI] [PubMed] [Google Scholar]
  11. Boshoff C., Schulz T. F., Kennedy M. M., Graham A. K., Fisher C., Thomas A., McGee J. O., Weiss R. A., O'Leary J. J. Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med. 1995 Dec;1(12):1274–1278. doi: 10.1038/nm1295-1274. [DOI] [PubMed] [Google Scholar]
  12. Boshoff C., Talbot S., Kennedy M., O'Leary J., Schulz T., Chang Y. HHV8 and skin cancers in immunosuppressed patients. Lancet. 1996 Feb 3;347(8997):338–339. doi: 10.1016/s0140-6736(96)90524-3. [DOI] [PubMed] [Google Scholar]
  13. Boshoff C., Whitby D., Hatziioannou T., Fisher C., van der Walt J., Hatzakis A., Weiss R., Schulz T. Kaposi's-sarcoma-associated herpesvirus in HIV-negative Kaposi's sarcoma. Lancet. 1995 Apr 22;345(8956):1043–1044. doi: 10.1016/s0140-6736(95)90780-7. [DOI] [PubMed] [Google Scholar]
  14. Bradley D. W., McCaustland K. A., Cook E. H., Schable C. A., Ebert J. W., Maynard J. E. Posttransfusion non-A, non-B hepatitis in chimpanzees. Physicochemical evidence that the tubule-forming agent is a small, enveloped virus. Gastroenterology. 1985 Mar;88(3):773–779. [PubMed] [Google Scholar]
  15. CHEARS W. C., Jr, ASHWORTH C. T. Electron microscopic study of the intestinal mucosa in Whipple's disease. Demonstration of encapsulated bacilliform bodies in the lesion. Gastroenterology. 1961 Aug;41:129–138. [PubMed] [Google Scholar]
  16. Centers for Disease Control and Prevention (CDC) Outbreak of acute illness--southwestern United States, 1993. MMWR Morb Mortal Wkly Rep. 1993 Jun 11;42(22):421–424. [PubMed] [Google Scholar]
  17. Centers for Disease Control and Prevention (CDC) Update: outbreak of hantavirus infection--southwestern United States, 1993. MMWR Morb Mortal Wkly Rep. 1993 Jun 18;42(23):441–443. [PubMed] [Google Scholar]
  18. Cesarman E., Chang Y., Moore P. S., Said J. W., Knowles D. M. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995 May 4;332(18):1186–1191. doi: 10.1056/NEJM199505043321802. [DOI] [PubMed] [Google Scholar]
  19. Cesarman E., Moore P. S., Rao P. H., Inghirami G., Knowles D. M., Chang Y. In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi's sarcoma-associated herpesvirus-like (KSHV) DNA sequences. Blood. 1995 Oct 1;86(7):2708–2714. [PubMed] [Google Scholar]
  20. Challoner P. B., Smith K. T., Parker J. D., MacLeod D. L., Coulter S. N., Rose T. M., Schultz E. R., Bennett J. L., Garber R. L., Chang M. Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7440–7444. doi: 10.1073/pnas.92.16.7440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Chang Y., Cesarman E., Pessin M. S., Lee F., Culpepper J., Knowles D. M., Moore P. S. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865–1869. doi: 10.1126/science.7997879. [DOI] [PubMed] [Google Scholar]
  22. Chang Y., Ziegler J., Wabinga H., Katangole-Mbidde E., Boshoff C., Schulz T., Whitby D., Maddalena D., Jaffe H. W., Weiss R. A. Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa. Uganda Kaposi's Sarcoma Study Group. Arch Intern Med. 1996 Jan 22;156(2):202–204. [PubMed] [Google Scholar]
  23. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359–362. doi: 10.1126/science.2523562. [DOI] [PubMed] [Google Scholar]
  24. Collandre H., Ferris S., Grau O., Montagnier L., Blanchard A. Kaposi's sarcoma and new herpesvirus. Lancet. 1995 Apr 22;345(8956):1043–1043. doi: 10.1016/s0140-6736(95)90779-3. [DOI] [PubMed] [Google Scholar]
  25. Cook S. D., Dowling P. C. Multiple sclerosis and viruses: an overview. Neurology. 1980 Jul;30(7 Pt 2):80–91. doi: 10.1212/wnl.30.7_part_2.80. [DOI] [PubMed] [Google Scholar]
  26. Deinhardt F., Holmes A. W., Wolfe L., Junge U. Transmission of viral hepatitis to nonhuman primates. Vox Sang. 1970 Sep-Oct;19(3):261–269. [PubMed] [Google Scholar]
  27. Dupin N., Grandadam M., Calvez V., Gorin I., Aubin J. T., Havard S., Lamy F., Leibowitch M., Huraux J. M., Escande J. P. Herpesvirus-like DNA sequences in patients with Mediterranean Kaposi's sarcoma. Lancet. 1995 Mar 25;345(8952):761–762. doi: 10.1016/s0140-6736(95)90642-8. [DOI] [PubMed] [Google Scholar]
  28. Elliott L. H., Ksiazek T. G., Rollin P. E., Spiropoulou C. F., Morzunov S., Monroe M., Goldsmith C. S., Humphrey C. D., Zaki S. R., Krebs J. W. Isolation of the causative agent of hantavirus pulmonary syndrome. Am J Trop Med Hyg. 1994 Jul;51(1):102–108. doi: 10.4269/ajtmh.1994.51.102. [DOI] [PubMed] [Google Scholar]
  29. Feinstone S. M., Alter H. J., Dienes H. P., Shimizu Y., Popper H., Blackmore D., Sly D., London W. T., Purcell R. H. Non-A, non-B hepatitis in chimpanzees and marmosets. J Infect Dis. 1981 Dec;144(6):588–598. doi: 10.1093/infdis/144.6.588. [DOI] [PubMed] [Google Scholar]
  30. Feinstone S. M., Kapikian A. Z., Purcell R. H., Alter H. J., Holland P. V. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med. 1975 Apr 10;292(15):767–770. doi: 10.1056/NEJM197504102921502. [DOI] [PubMed] [Google Scholar]
  31. Fredricks D. N., Relman D. A. Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates. Clin Microbiol Rev. 1996 Jan;9(1):18–33. doi: 10.1128/cmr.9.1.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Graham D. Y., Markesich D. C., Kalter D. C., Moss M. T., Hermon-Taylor J., el-Zaatari F. A. Mycobacterial aetiology of sarcoidosis. Lancet. 1992 Jul 4;340(8810):52–53. doi: 10.1016/0140-6736(92)92465-r. [DOI] [PubMed] [Google Scholar]
  33. Harrington D. S., Weisenburger D. D., Purtilo D. T. Epstein-Barr virus--associated lymphoproliferative lesions. Clin Lab Med. 1988 Mar;8(1):97–118. [PubMed] [Google Scholar]
  34. He L. F., Alling D., Popkin T., Shapiro M., Alter H. J., Purcell R. H. Determining the size of non-A, non-B hepatitis virus by filtration. J Infect Dis. 1987 Oct;156(4):636–640. doi: 10.1093/infdis/156.4.636. [DOI] [PubMed] [Google Scholar]
  35. Karayiannis P., Petrovic L. M., Fry M., Moore D., Enticott M., McGarvey M. J., Scheuer P. J., Thomas H. C. Studies of GB hepatitis agent in tamarins. Hepatology. 1989 Feb;9(2):186–192. doi: 10.1002/hep.1840090204. [DOI] [PubMed] [Google Scholar]
  36. Knowles D. M., Inghirami G., Ubriaco A., Dalla-Favera R. Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus. Blood. 1989 Feb 15;73(3):792–799. [PubMed] [Google Scholar]
  37. Koehler J. E., Glaser C. A., Tappero J. W. Rochalimaea henselae infection. A new zoonosis with the domestic cat as reservoir. JAMA. 1994 Feb 16;271(7):531–535. doi: 10.1001/jama.271.7.531. [DOI] [PubMed] [Google Scholar]
  38. Koehler J. E., Quinn F. D., Berger T. G., LeBoit P. E., Tappero J. W. Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. N Engl J Med. 1992 Dec 3;327(23):1625–1631. doi: 10.1056/NEJM199212033272303. [DOI] [PubMed] [Google Scholar]
  39. Ksiazek T. G., Peters C. J., Rollin P. E., Zaki S., Nichol S., Spiropoulou C., Morzunov S., Feldmann H., Sanchez A., Khan A. S. Identification of a new North American hantavirus that causes acute pulmonary insufficiency. Am J Trop Med Hyg. 1995 Feb;52(2):117–123. doi: 10.4269/ajtmh.1995.52.117. [DOI] [PubMed] [Google Scholar]
  40. Kuo G., Choo Q. L., Alter H. J., Gitnick G. L., Redeker A. G., Purcell R. H., Miyamura T., Dienstag J. L., Alter M. J., Stevens C. E. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989 Apr 21;244(4902):362–364. doi: 10.1126/science.2496467. [DOI] [PubMed] [Google Scholar]
  41. Kurtzke J. F. Geography in multiple sclerosis. J Neurol. 1977 Apr 28;215(1):1–26. doi: 10.1007/BF00312546. [DOI] [PubMed] [Google Scholar]
  42. Kurtzke J. F. On the fine structure of the distribution of multiple sclerosis. Acta Neurol Scand. 1967;43(3):257–282. doi: 10.1111/j.1600-0404.1967.tb05733.x. [DOI] [PubMed] [Google Scholar]
  43. Kurtzke J. F. Some epidemiologic features compatible with an infectious origin for multiple sclerosis. Int Arch Allergy Appl Immunol. 1969;36(Suppl):59–82. [PubMed] [Google Scholar]
  44. Lane D. J., Stahl D. A., Olsen G. J., Heller D. J., Pace N. R. Phylogenetic analysis of the genera Thiobacillus and Thiomicrospira by 5S rRNA sequences. J Bacteriol. 1985 Jul;163(1):75–81. doi: 10.1128/jb.163.1.75-81.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. LeBoit P. E., Berger T. G., Egbert B. M., Yen T. S., Stoler M. H., Bonfiglio T. A., Strauchen J. A., English C. K., Wear D. J. Epithelioid haemangioma-like vascular proliferation in AIDS: manifestation of cat scratch disease bacillus infection? Lancet. 1988 Apr 30;1(8592):960–963. doi: 10.1016/s0140-6736(88)91779-5. [DOI] [PubMed] [Google Scholar]
  46. LeDuc J. W. Epidemiology of Hantaan and related viruses. Lab Anim Sci. 1987 Aug;37(4):413–418. [PubMed] [Google Scholar]
  47. Levy J. A. A new human herpesvirus: KSHV or HHV8? Lancet. 1995 Sep 23;346(8978):786–786. doi: 10.1016/s0140-6736(95)91611-3. [DOI] [PubMed] [Google Scholar]
  48. Lin J. C., Lin S. C., Mar E. C., Pellett P. E., Stamey F. R., Stewart J. A., Spira T. J. Is Kaposi's-sarcoma-associated herpesvirus detectable in semen of HIV-infected homosexual men? Lancet. 1995 Dec 16;346(8990):1601–1602. doi: 10.1016/s0140-6736(95)91931-7. [DOI] [PubMed] [Google Scholar]
  49. Lisitsyn N. A., Lisitsina N. M., Dalbagni G., Barker P., Sanchez C. A., Gnarra J., Linehan W. M., Reid B. J., Wigler M. H. Comparative genomic analysis of tumors: detection of DNA losses and amplification. Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):151–155. doi: 10.1073/pnas.92.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Lisitsyn N., Lisitsyn N., Wigler M. Cloning the differences between two complex genomes. Science. 1993 Feb 12;259(5097):946–951. doi: 10.1126/science.8438152. [DOI] [PubMed] [Google Scholar]
  51. Luppi M., Barozzi P., Maiorana A., Marasca R., Torelli G. Human herpesvirus 6 infection in normal human brain tissue. J Infect Dis. 1994 Apr;169(4):943–944. doi: 10.1093/infdis/169.4.943. [DOI] [PubMed] [Google Scholar]
  52. Moore P. S., Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med. 1995 May 4;332(18):1181–1185. doi: 10.1056/NEJM199505043321801. [DOI] [PubMed] [Google Scholar]
  53. Moore P. S., Gao S. J., Dominguez G., Cesarman E., Lungu O., Knowles D. M., Garber R., Pellett P. E., McGeoch D. J., Chang Y. Primary characterization of a herpesvirus agent associated with Kaposi's sarcomae. J Virol. 1996 Jan;70(1):549–558. doi: 10.1128/jvi.70.1.549-558.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Moore P. S., Kingsley L. A., Holmberg S. D., Spira T., Gupta P., Hoover D. R., Parry J. P., Conley L. J., Jaffe H. W., Chang Y. Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma. AIDS. 1996 Feb;10(2):175–180. doi: 10.1097/00002030-199602000-00007. [DOI] [PubMed] [Google Scholar]
  55. Nichol S. T., Spiropoulou C. F., Morzunov S., Rollin P. E., Ksiazek T. G., Feldmann H., Sanchez A., Childs J., Zaki S., Peters C. J. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science. 1993 Nov 5;262(5135):914–917. doi: 10.1126/science.8235615. [DOI] [PubMed] [Google Scholar]
  56. Peterman T. A., Jaffe H. W., Beral V. Epidemiologic clues to the etiology of Kaposi's sarcoma. AIDS. 1993 May;7(5):605–611. doi: 10.1097/00002030-199305000-00001. [DOI] [PubMed] [Google Scholar]
  57. Rady P. L., Yen A., Rollefson J. L., Orengo I., Bruce S., Hughes T. K., Tyring S. K. Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients. Lancet. 1995 May 27;345(8961):1339–1340. doi: 10.1016/s0140-6736(95)92538-4. [DOI] [PubMed] [Google Scholar]
  58. Rangan S. R., Martin L. N., Enright F. M., Abee C. R. Herpesvirus saimiri-induced lymphoproliferative disease in howler monkeys. J Natl Cancer Inst. 1977 Jul;59(1):165–171. doi: 10.1093/jnci/59.1.165. [DOI] [PubMed] [Google Scholar]
  59. Regnery R. L., Anderson B. E., Clarridge J. E., 3rd, Rodriguez-Barradas M. C., Jones D. C., Carr J. H. Characterization of a novel Rochalimaea species, R. henselae sp. nov., isolated from blood of a febrile, human immunodeficiency virus-positive patient. J Clin Microbiol. 1992 Feb;30(2):265–274. doi: 10.1128/jcm.30.2.265-274.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Regnery R. L., Olson J. G., Perkins B. A., Bibb W. Serological response to "Rochalimaea henselae" antigen in suspected cat-scratch disease. Lancet. 1992 Jun 13;339(8807):1443–1445. doi: 10.1016/0140-6736(92)92032-b. [DOI] [PubMed] [Google Scholar]
  61. Regnery R., Tappero J. Unraveling mysteries associated with cat-scratch disease, bacillary angiomatosis, and related syndromes. Emerg Infect Dis. 1995 Jan-Mar;1(1):16–21. doi: 10.3201/eid0101.950103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Relman D. A., Loutit J. S., Schmidt T. M., Falkow S., Tompkins L. S. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. N Engl J Med. 1990 Dec 6;323(23):1573–1580. doi: 10.1056/NEJM199012063232301. [DOI] [PubMed] [Google Scholar]
  63. Relman D. A., Schmidt T. M., MacDermott R. P., Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992 Jul 30;327(5):293–301. doi: 10.1056/NEJM199207303270501. [DOI] [PubMed] [Google Scholar]
  64. Relman D. A. The identification of uncultured microbial pathogens. J Infect Dis. 1993 Jul;168(1):1–8. doi: 10.1093/infdis/168.1.1. [DOI] [PubMed] [Google Scholar]
  65. Renne R., Zhong W., Herndier B., McGrath M., Abbey N., Kedes D., Ganem D. Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med. 1996 Mar;2(3):342–346. doi: 10.1038/nm0396-342. [DOI] [PubMed] [Google Scholar]
  66. Roizman B. New viral footprints in Kaposi's sarcoma. N Engl J Med. 1995 May 4;332(18):1227–1228. doi: 10.1056/NEJM199505043321810. [DOI] [PubMed] [Google Scholar]
  67. Rowley A. H., Wolinsky S. M., Relman D. A., Sambol S. P., Sullivan J., Terai M., Shulman S. T. Search for highly conserved viral and bacterial nucleic acid sequences corresponding to an etiologic agent of Kawasaki disease. Pediatr Res. 1994 Nov;36(5):567–571. doi: 10.1203/00006450-199411000-00003. [DOI] [PubMed] [Google Scholar]
  68. Schalling M., Ekman M., Kaaya E. E., Linde A., Biberfeld P. A role for a new herpes virus (KSHV) in different forms of Kaposi's sarcoma. Nat Med. 1995 Jul;1(7):707–708. doi: 10.1038/nm0795-707. [DOI] [PubMed] [Google Scholar]
  69. Schaluder G. G., Dawson G. J., Simons J. N., Pilot-Matias T. J., Gutierrez R. A., Heynen C. A., Knigge M. F., Kurpiewski G. S., Buijk S. L., Leary T. P. Molecular and serologic analysis in the transmission of the GB hepatitis agents. J Med Virol. 1995 May;46(1):81–90. doi: 10.1002/jmv.1890460117. [DOI] [PubMed] [Google Scholar]
  70. Scott J. K., Smith G. P. Searching for peptide ligands with an epitope library. Science. 1990 Jul 27;249(4967):386–390. doi: 10.1126/science.1696028. [DOI] [PubMed] [Google Scholar]
  71. Simons J. N., Leary T. P., Dawson G. J., Pilot-Matias T. J., Muerhoff A. S., Schlauder G. G., Desai S. M., Mushahwar I. K. Isolation of novel virus-like sequences associated with human hepatitis. Nat Med. 1995 Jun;1(6):564–569. doi: 10.1038/nm0695-564. [DOI] [PubMed] [Google Scholar]
  72. Simons J. N., Pilot-Matias T. J., Leary T. P., Dawson G. J., Desai S. M., Schlauder G. G., Muerhoff A. S., Erker J. C., Buijk S. L., Chalmers M. L. Identification of two flavivirus-like genomes in the GB hepatitis agent. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3401–3405. doi: 10.1073/pnas.92.8.3401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Slater L. N., Welch D. F., Hensel D., Coody D. W. A newly recognized fastidious gram-negative pathogen as a cause of fever and bacteremia. N Engl J Med. 1990 Dec 6;323(23):1587–1593. doi: 10.1056/NEJM199012063232303. [DOI] [PubMed] [Google Scholar]
  74. Stoler M. H., Bonfiglio T. A., Steigbigel R. T., Pereira M. An atypical subcutaneous infection associated with acquired immune deficiency syndrome. Am J Clin Pathol. 1983 Nov;80(5):714–718. doi: 10.1093/ajcp/80.5.714. [DOI] [PubMed] [Google Scholar]
  75. Strathdee S. A., Veugelers P. J., Moore P. S. The epidemiology of HIV-associated Kaposi's sarcoma: the unraveling mystery. AIDS. 1996;10 (Suppl A):S51–S57. [PubMed] [Google Scholar]
  76. Tabor E., Peterson D. A., April M., Seeff L. B., Gerety R. J. Transmission of human non-A, non-B hepatitis to chimpanzees following failure to transmit GB agent hepatitis. J Med Virol. 1980;5(2):103–108. doi: 10.1002/jmv.1890050202. [DOI] [PubMed] [Google Scholar]
  77. Welch D. F., Pickett D. A., Slater L. N., Steigerwalt A. G., Brenner D. J. Rochalimaea henselae sp. nov., a cause of septicemia, bacillary angiomatosis, and parenchymal bacillary peliosis. J Clin Microbiol. 1992 Feb;30(2):275–280. doi: 10.1128/jcm.30.2.275-280.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Whitby D., Howard M. R., Tenant-Flowers M., Brink N. S., Copas A., Boshoff C., Hatzioannou T., Suggett F. E., Aldam D. M., Denton A. S. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet. 1995 Sep 23;346(8978):799–802. doi: 10.1016/s0140-6736(95)91619-9. [DOI] [PubMed] [Google Scholar]
  79. Wilson K. H., Blitchington R., Frothingham R., Wilson J. A. Phylogeny of the Whipple's-disease-associated bacterium. Lancet. 1991 Aug 24;338(8765):474–475. doi: 10.1016/0140-6736(91)90545-z. [DOI] [PubMed] [Google Scholar]
  80. Zuckerman A. J. The new GB hepatitis viruses. Lancet. 1995 Jun 10;345(8963):1453–1454. doi: 10.1016/s0140-6736(95)91032-8. [DOI] [PubMed] [Google Scholar]

Articles from Emerging Infectious Diseases are provided here courtesy of Centers for Disease Control and Prevention

RESOURCES