Our interest in virus discovery began in 1988. In 2010, we are continuing this quest. Read about our ideas for the Global Virus Discovery Program in Kenya.
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:
- The first description of HHV-6 pneumonitis in an immunocompetent adult (1).
- The first description of fatal HHV-6 pneumonitis in immunocompromised patients (2).
- 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).
- The first demonstration of HHV-6's ability to block the differentiation of both bone marrow stem cells (6)
and monocytes (7).
- The first description of fatal HHV-6 encephalitis in an immunocompromised patient (8).
- The first description of fatal congenital infection by HHV-6 in an infant (9).
- The first demonstration of disseminated active infection by HHV-6 in patients with AIDS (10).
- The first demonstration of active HHV-6 infection in the central nervous system (CNS) of patients with accompanying demyelination in patients with AIDS (11).
- 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).
- The first description of fatal HHV-6 encephalitis in an HIV infected infant (13).
- The first comprehensive studies of the pathogenicity of HHV-6 in liver transplant recipients (14-18)
- The first demonstration that subacute HHV-6 encephalitis in an immunocompetent individual can strongly mimic multiple sclerosis (19).
- One of the first demonstrations of a role for HHV-6 in the pathogenesis of MS (20,21).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Knox KK and Carrigan DR. (1994). Disseminated active HHV-6 infections in patients with AIDS. Lancet 343:577-578.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.