Human herpesvirus 6 (HHV-6), discovered 4 years ago, is most closely related to CMV. Serologic studies indicate that nearly everyone becomes infected early in childhood, probably resulting in lifelong latency. HHV-6 is readily detected in peripheral blood mononuclear cells (PBMC) from children with roseola and in a subset of immunocompromised individuals. This proposal describes studies that will examine the time course and anatomic sites of HHV-6 infection, reactivation and latency in 3 immunosuppressed groups: the largest group will be bone marrow transplant (BMT) patients, and 2 smaller groups are comprised of liver transplant and heart transplant patients (Specific Aim 1). Preliminary data suggests that BMT patients with lung disease have HHV-6 in lung tissue. This finding will be expanded to investigate the etiologic role of HHV-6 in BMT patients with lung disease (Specific Aim 2). The subjects will have normal age and sex matched controls, who will also serve to better define the natural history of HHV-6 infection in immunocompetent people (Specific Aim 3). The prevalence of reinfection versus reactivation in BMT patients will be studied after developing a polymerase chain reaction (PCR) method for strain specific identification of HHV-6 in clinical samples (Specific Aim 4). Saliva, PBMC, urine, and biopsy tissue will be collected on a regular basis over 6 months and screened using semi-quantitative HHV-6 specific PCR. Positive samples will be further examined using HHV-6 RNA directed PCR, in situ hybridization and immunocytochemistry. HHV-6 culture will be performed in selected cases. An HHV-6 EIA serology will be used to document the serologic status at each time point when other samples are taken. The proposed studies will better define the natural history of HHV- 6 infections in immunocompromised and normal individuals. Specific etiologic relationships between HHV-6 infection and clinical disease will be sought in the immunocompromised subjects, who have demonstrated a propensity for exhibiting symptoms from other herpesvirus infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI030648-03
Application #
3455719
Study Section
Virology Study Section (VR)
Project Start
1991-01-01
Project End
1995-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105
Cone, R W; Huang, M L; Corey, L et al. (1999) Human herpesvirus 6 infections after bone marrow transplantation: clinical and virologic manifestations. J Infect Dis 179:311-8
Cone, R W; Huang, M L; Hackman, R C et al. (1996) Coinfection with human herpesvirus 6 variants A and B in lung tissue. J Clin Microbiol 34:877-81
Cone, R W; Huang, M L; Ashley, R et al. (1993) Human herpesvirus 6 DNA in peripheral blood cells and saliva from immunocompetent individuals. J Clin Microbiol 31:1262-7
Cone, R W; Hackman, R C; Huang, M L et al. (1993) Human herpesvirus 6 in lung tissue from patients with pneumonitis after bone marrow transplantation. N Engl J Med 329:156-61
Fairfax, M R; Metcalf, M A; Cone, R W (1991) Slow inactivation of dry PCR templates by UV light. PCR Methods Appl 1:142-3