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Human Herpesvirus-6 in Transplantation: An Emerging Pathogen

BACKGROUND: Human Herpesvirus 6 was previously demonstrated to infecthuman oligodendroglial precursor cells (OPCs) in vitro causing cell cycle arrest and premature differentiation with consequent loss of the precursor pool.OBJECTIVES: To develop an in vitro murine OPC model to study the cell cycle and differentiation effects of HHV-6 in more readily available, genetically well-defined cells free of the risk of contamination with human herpesviruses. [1] reported a selective reactivation of human herpesvirus 6 (HHV-6) variant A in critically ill immunocompetent patients. HHV-6 variant B causes the common childhood disease exhanthem subitum, and although the pathologic characteristics for HHV-6 variant A are less well defined, HHV-6A has been suggested to be more neurotropic. For that purpose, susceptibility assays have to fulfill various criteria: standardization, easy use, specificity, and reproducibility of results. The virus is pathogenic in the post transplantation period and may be a cofactor in the progression of HIV disease. The genome was detectable in PBMC of 22 of 31 (71%) patients tested. In addition, specimens such as organ biopsies or body cavity effusions were examined for HHV-6 DNA whenever infectious complications, GvHD or further compromising conditions were suspected regardless of whether the blood sample was positive for HHV-6 or not.

To clarify the incidence and clinical relevance of active HHV-6 infection, serial titers of plasma HHV6 DNA were determined for 50 allogeneic SCT recipients, using real-time polymerase chain reaction. However, a U51-specific antiserum had no virus-neutralizing activity, suggesting that U51 may not be involved in the initial interaction between the virus particle and host cell. Prophylaxis of human herpesvirus-6 infection is feasible in transplant recipients, but this issue must be studied further. Conclusion: Human herpesvirus-6 can be a pathogen in transplant recipients. Prompt recognition of disease associated with human herpesvirus-6 is important because this virus is susceptible to currently available antiviral agents. The mean duration of illness was 6 days, and the most common complication of primary HHV-6 infection was febrile seizures; these occurred in 13 of the children studied 4. Other complications of primary HHV-6B infection include hepatitis, meningitis, fatal hemophagocytic syndrome, and fatal disseminated infection (7, 22, 23, 39).

Our work is unique in demonstrating type I IFN signaling defects in HHV-6B-infected cells and highlights a major biological difference between HHV-6 variants. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Patients had twice-weekly plasma specimens tested for HHV-6 through day 84 after CBT. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.