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History

Our interest in virus discovery began in 1988. In 2014, we are continuing this quest in our new company, Coppe Labs.

Late in 1988, a positive but life-changing event occurred in the laboratory of Dr. Knox and Dr. Carrigan in the Department of Pathology at the Medical College of Wisconsin. They were asked by a fellow in the HIV/AIDS Program to try and isolate HIV from a patient's peripheral blood.

The patient was an enigma. He was clinically suffering from AIDS (severe T lymphopenia, mental status changes, and life-threatening opportunistic infections), but he was seronegative for HIV and was negative for the HIVp24 antigen in his serum. A standard HIV isolation culture was established, but no HIV could be detected throughout the course of the culture.

However, an unusual cytopathic agent was isolated (number 1 below). Standard virologic methods were used to confirm that the agent was a virus, and by electron microscopy this agent was identified as a member of the herpesvirus family. Further studies, in collaboration with Robert Gallo's laboratory at the National Cancer Institute, confirmed that the virus was a newly described form of herpesvirus termed human herpesvirus six (HHV-6). The surprise isolation of this almost unknown virus provided the inspiration for Drs. Knox and Carrigan's Program for Virus Discovery.

In collaboration with a number of physicians and other researchers, the Program embarked on a series of investigations that have led to a remarkable period of discovery as to the biologic and pathogenic potentials of HHV-6.

These discoveries include:

  1. The first description of HHV-6 pneumonitis in an immunocompetent adult (1).
  2. The first description of fatal HHV-6 pneumonitis in immunocompromised patients (2).
  3. The first description of the ability of HHV-6 to cause potentially fatal bone marrow suppression in both immunocompetent and immunocompromised individuals (3,4,5).
  4. The first demonstration of HHV-6's ability to block the differentiation of both bone marrow stem cells (6) and monocytes (7).
  5. The first description of fatal HHV-6 encephalitis in an immunocompromised patient (8).
  6. The first description of fatal congenital infection by HHV-6 in an infant (9).
  7. The first demonstration of disseminated active infection by HHV-6 in patients with AIDS (10).
  8. The first demonstration of active HHV-6 infection in the central nervous system (CNS) of patients with accompanying demyelination in patients with AIDS (11).
  9. The first demonstration of active and widespread lymphoid tissue infections with HHV-6 in both patients with AIDS and in individuals with HIV infection but normal levels of CD4+ lymphocytes (12).
  10. The first description of fatal HHV-6 encephalitis in an HIV infected infant (13).
  11. The first comprehensive studies of the pathogenicity of HHV-6 in liver transplant recipients (14-18).
  12. The first demonstration that subacute HHV-6 encephalitis in an immunocompetent individual can strongly mimic multiple sclerosis (19).
  13. One of the first demonstrations of a role for HHV-6 in the pathogenesis of MS (20,21).

Publications

  1. Russler SK, Tapper MA, Knox KK, Liepins A, and Carrigan DR. (1991). Pneumonitis associated with coinfection by human herpesvirus six and legionella in an immunocompetent adult. Amer J Pathol 138:1405-1411.
  2. Carrigan DR, Drobyski WR, Russler SK, Tapper MA, Knox KK, and Ash RC. (1991). Interstitial pneumonitis associated with human herpesvirus six (HHV-6) infection in marrow transplant patients. Lancet 338:147-149.
  3. Drobyski WR, Dunne WM, Burd EM, Knox KK, Ash RC, Horowitz MM, Flomenberg N, and Carrigan DR. (1993). Human herpesvirus 6 (HHV-6) infection in allogeneic bone marrow transplant recipients: I. Evidence for a marrow suppressive role for HHV-6 in vivo. J Infect Dis 167:735-739.
  4. Carrigan DR, Knox KK. (1994). Human herpesvirus six (HHV-6) isolation from bone marrow: HHV-6 associated bone marrow suppression in bone marrow transplant patients. Blood, 84:3307-3310.
  5. Gompels UA, Luxton J, Knox KK and Carrigan DR. (1994). Chronic bone marrow suppression in an immunocompetent adult with persistent marrow infection by human herpesvirus 6. Lancet 343:735-736.
  6. Knox KK and Carrigan DR. (1992). In vitro suppression of marrow progenitor cell differentiation by human herpesvirus six infection. J Infect Dis 165:925-929.
  7. Burd EM, Knox KK, and Carrigan DR. (1993). Human herpesvirus six mediated suppression of growth factor induced macrophage maturation in human bone marrow cultures. Blood 81:1645-1650.
  8. Drobyski WR, Knox KK, Majewski D, and Carrigan DR. (1994). Fatal encephalitis due to variant B human herpesvirus 6 infection in a bone marrow transplant recipient. N Engl J Med 330:1356-1360.
  9. Knox KK, Pietryga D, Franciosi R, and Carrigan DR. (1995). Progressive immunodeficiency and fatal pneumonitis associated with HHV-6 infection in an infant. Clin Infect Dis, 20:406-413.
  10. Knox KK and Carrigan DR. (1994). Disseminated active HHV-6 infections in patients with AIDS. Lancet 343:577-578.
  11. Knox KK, Carrigan DR. (1995). Active human herpesvirus six (HHV-6) infection of the central nervous system in patients with AIDS. J Immune Defic Syndr and Hum Retrovir 9:69-73.
  12. Knox KK and Carrigan DR. (1996). Active HHV-6 infection in the lymph nodes of HIV infected patients: In vitro evidence that HHV-6 can break HIV latency. J Acquired Immune Defic Syndr and Hum Retrovirol, 11:370-378.
  13. Knox KK, Harrington D and Carrigan DR. (1995). Fulminant human herpesvirus six (HHV-6) encephalitis in an HIV infected infant. J Med Virol, 45:288-292.
  14. Singh N, Gayowski T, Carrigan DR, and Singh J. (1995). Human herpesvirus 6 associated febrile dermatosis with thrombocytopenia and encephalopathy in a liver transplant recipient. Transplantation, 60:1355-1357.
  15. Singh N, Gayowski T and Carrigan DR. (1997). Human herpesvirus six (HHV-6) infection in liver transplant recipients: Documentation of pathogenicity. Transplantation 64, 674-678.
  16. Rogers J, Singh N, Carrigan DR, Rohal S, Kusne S, Knox KK, Wagener MM and Fung JJ. (2000). Human herpesvirus 6 in liver transplant recipients: role in pathogenesis of fungal infections, neurologic complications and outcome. Transplantation, 69:2566-2573.
  17. Singh N, Husain S, Carrigan DR, Knox KK, Weck KE, Wagener MM and Gayowski T. (2001). Impact of human herpesvirus six viremia on the frequency and severity of recurrent hepatitis C virus hepatitis in liver transplant recipients. Clin Transplant, 16:92-96.
  18. Singh N, Bentlejewski, Carrigan DR, Gayowski T, Knox KK and Zeevi A. (2002). Persistent lack of human herpesvirus 6 specific T-helper cell response in liver transplant recipients. Transpl Infect Dis, 4:59-63.
  19. Carrigan DR, Harrington D and Knox KK. (1996). Subacute leukoencephalitis caused by CNS infection with human herpesvirus six manifesting as acute multiple sclerosis. Neurology, 47:145-148.
  20. Knox KK, Brewer JH, Harrington DJ, Henry JM, and Carrigan DR. (2000). Human herpesvirus six and multiple sclerosis: systemic active infections in patients with early disease. Clin Infect Dis, 31:894-903.
  21. Knox KK and Carrigan DR. (2001). Active human herpesvirus six viremia in patients with multiple sclerosis. Genes and Viruses in Multiple Sclerosis; Elsevier Science B.V. Amsterdam, The Netherlands, pp. 185-194.