No abstract

In order to determine whether mixed infections of human herpesvirus 6B (HHV-6B) occur in immunocompetent and immunocompromised individuals, we examined the copy numbers of telomeric repeat sequences (TRS) of clinical isolates. In clinical isolates obtained from patients with exanthem subitum caused by primary HHV-6B infection, PCR products with HHV-6B TRS ranging between 400 and 800 bp were amplified. PCR products of various sizes were amplified in four clinical isolates from druginduced hypersensitivity syndrome (DIHS) patients and 15 isolates from hematopoietic stem cell transplant (HSCT) recipients with HHV-6B reactivation. Based on the sequence analysis of the PCR products, the copy numbers of TRS in DIHS and HSCT patients were between 42 and 82 and 22 and >90, respectively. For two of the HSCT recipients, HHV-6B TRS PCR products of different sizes were detected in several isolates from each patient, which suggests mixed HHV-6B infections. In two of the posttransplant HHV-6B encephalitis patients, the sizes of the TRS nested PCR products amplified from the reactivated virus detected in the central nervous system differed from those of the virus detected in initial isolates from peripheral blood mononuclear cells. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for the discrimination of HHV-6B clinical isolates. Additionally, mixed HHV-6B infections occurred in HSCT recipients, and in some cases, compartmentalization of the HHV-6B strains to the central nervous system versus the blood compartment occurred in posttransplant HHV-6B encephalitis patients. Primary human herpesvirus 6B (HHV-6B) infection presenting as exanthem subitum (ES) (1, 2) is considered a benign febrile illness and rarely causes neurological complications, such as febrile convulsion and encephalitis (3, 4). In addition to the primary infection, HHV-6 reactivation may be associated with acute graftversus-host disease (5-8), graft rejection (9), and encephalitis (10-13) in transplant recipients. Moreover, the virus can be reactivated in patients with drug-induced hypersensitivity syndrome (DIHS), which is a severe form of drug allergy that is characterized by fever, skin rash, lymphadenopathy, hepatitis, and leukocytosis (14-16). Active HHV-6B infection generally occurs only once throughout life (at the time of the primary infection) in immunocompetent individuals, but it may occur several times in transplant recipients (8) or DIHS patients (17). Frequent HHV-6B reactivation, as evidenced by the repeated isolation of the virus during an active viral infection, was observed in hematopoietic stem cell transplant (HSCT) recipients (8, 18).Previous reports detected mixed infections with multiple cytomegalovirus (CMV) strains in the same human herpesvirus subfamily (Betaherpesvirinae subfamily) as HHV-6B in a variety of patient populations, including immunocompetent and immunocompromised patients (19)(20)(21)(22). Furthermore, other studies have suggested that the genotype of the virus may be associate...