Human herpesvirus 6 (HHV-6) infection was studied in 82 bone marrow transplant (BMT) recipients (72 allogeneic, 10 autologous). All recipients and 30 donors were seropositive for HHV-6 antibody at the time of bone marrow transplantation. Thirty-one recipients (37.8%) had HHV-6 viremia 2-4 weeks after transplantation. The incidence of HHV-6 viremia was significantly higher among allogeneic BMT recipients than in autologous BMT recipients (P=.011). Therefore, the following analyses of allogeneic BMT recipients were carried out (n=72). Geometric mean antibody titers (log(10)) were significantly higher in recipients without viremia than in those with viremia (1.84+/-0.39 vs. 1.61+/-0.42; P=.022). Logistic regression analysis demonstrated that leukemia or lymphoma is an independent risk factor (P=.031) for HHV-6 viremia. Rash occurring within 1 month after transplantation was observed in 17 (54.8%) of 31 recipients with HHV-6 viremia but in only 8 (19.5%) of 41 recipients without HHV-6 viremia (P=.001).

Rotavirus antigenemia is frequently observed in a patient's serum during the acute phase, and viral antigen levels change dramatically during the acute phase of the illness. Because patients with fever had higher rotavirus antigen levels, antigenemia severity might contribute to fever. The host immune response plays an important role in controlling antigenemia levels.

A mutation abolishing cytosolic glutamine synthetase1;2 (GS1;2) activity impairs assimilation of ammonium into glutamine in both roots and basal portions of shoots, and severely decreases axillary bud outgrowth (tillering) in mutant rice seedlings. Although the gs1;2 mutant phenotype is independent of strigolactone, which inhibits tillering, it also demonstrates glutamine- or related metabolite-responsive biosynthesis of cytokinin (CK), which promotes tillering. Here, we examined the connection between GS1;2 and CK biosynthesis during tillering, focusing on basal portions of the shoots as well as apical and axillary bud meristems in the gs1;2 mutant. Despite a sufficient ammonium supply, decreases in precursor CK contents and a decrease in ammonium assimilation into glutamine were observed in basal portions of mutant shoots. Reintroducing expression of OsGS1;2 cDNA driven by its own promoter restored precursor CK contents and ammonium assimilation to wild-type levels. In basal portions of the shoots, glutamine-responsive adenosine phosphate-isopentenyltransferase4 (OsIPT4), which is also predominant in rice roots, was the predominant isogene for IPT, which synthesizes CK. Cell-specific expression of OsIPT4 in phloem companion cells in nodal vascular anastomoses connected to the axillary bud vasculature also decreased in the gs1;2 mutant. Expression of CK-responsive type-A response regulator genes as local indicators of active CKs was also abolished in the axillary bud meristem of the mutant. These results suggest that the lack of GS1;2 activity decreased levels of glutamine or a related metabolite required for CK biosynthesis, causing a deficiency in active CK in the axillary bud meristem necessary for tillering.

Summary:We investigated whether a causal relationship exists between human herpesvirus 6 (HHV-6) and skin rash resembling acute graft-versus-host disease (GVHD) following bone marrow transplantation (BMT). Isolation of HHV-6 was used to monitor active HHV-6 infection in this study. We analyzed 25 episodes of skin rash in 22 recipients. All recipients were seropositive for HHV-6 before BMT. The onset of skin rash started prior to 30 days post transplantation (group A) in 15 of 25 cases, but after that (group B) in the remaining 10 cases. Twenty-five skin tissue samples were obtained from 22 recipients. The HHV-6 genome was detected in four of 15 skin samples from group A, but not detected in those from group B. HHV-6 was isolated from 11 of 22 recipients around 2 to 3 weeks after BMT (range 14 to 28 days after BMT). HHV-6 was isolated at a time between 10 days before and after the onset of skin rash (skin rash-related viremia) in nine cases in group A. Meanwhile, no skin rash-related viremia was observed in group B. Of the four recipients with positive detection of HHV-6 genome in their skin tissue (group A), two had HHV-6 viremia at the same time. The association between the timing of HHV-6 infection and the onset of skin rash was analyzed statistically. HHV-6 viremia (skin rash-related viremia) was found in nine of 15 (60%) cases in group A, compared with none of 10 (0%) cases in group B. This difference was statistically significant (P = 0.008). Moreover, HHV-6 infection (skin rash-related viremia and/or positive detection of HHV-6 DNA in skin tissue) was demonstrated in 11 of 15 (73.3%) cases in group A, compared with none of 10 (0%) cases in group B (P = 0.001). Thus, this study suggests that HHV-6 may be involved in the development of skin rash in the first month after allogeneic BMT. Bone Marrow Transplantation (2001) 28, 77-81.

A novel nucleic acid amplification method, termed loop-mediated isothermal amplification (LAMP), which amplifies DNA with high specificity, efficiency, and rapidity under isothermal conditions, may be a valuable tool for the rapid detection of infectious agents. LAMP was developed for human herpesvirus 6 (HHV-6), and its reliability was evaluated in this study. Although LAMP products were detected in HHV-6 B and HHV-6 A DNA, they were not detected in HHV-7 and human cytomegalovirus DNA. The sensitivity of the original HHV-6 LAMP protocol was 50 copies/tube. In order to increase the method's sensitivity, HHV-6 LAMP was modified by increasing the primer concentration. As a result of the modification, sensitivity increased to 25 copies/tube. After these initial validation studies, 13 patients with fever were tested for HHV-6 by viral isolation, serological analysis, and HHV-6 LAMP. In three of the eight patients with primary HHV-6 infection, HHV-6 DNA was detected in whole blood by the original HHV-6 LAMP protocol in not only the acute phase but also the convalescent phase. HHV-6 DNA was detected by modified HHV-6 LAMP in all eight plasma samples collected in the acute phase; however, no HHV-6 DNA was detected in plasma samples collected in the convalescent phase. Although HHV-6 DNA was detected in both the acute and convalescent phases of whole-blood samples in patients with past HHV-6 infection, it was not detected in plasma samples that did not contain latent viral DNA. Thus, detection of HHV-6 DNA in plasma by using this modified HHV-6 LAMP protocol is appropriate for diagnosis of active HHV-6 infection.