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KOICHI YAMANISHI - One of the best experts on this subject based on the ideXlab platform.
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Human Herpesvirus 6 induces mvb formation and virus egress occurs by an exosomal release pathway
Traffic, 2008Co-Authors: Yasuko Mori, Masato Koike, Eiko Moriishi, Akiko Kawabata, Huamin Tang, Hiroko Oyaizu, Yasuo Uchiyama, KOICHI YAMANISHIAbstract:The final envelopment of most Herpesviruses occurs at Golgi or post-Golgi compartments, such as the trans Golgi network (TGN); however, the final envelopment site of Human Herpesvirus 6 (HHV-6) is uncertain. In this study, we found novel pathways for HHV-6 assembly and release from T cells that differed, in part, from those of alphaHerpesviruses. Electron microscopy showed that late in infection, HHV-6-infected cells were larger than uninfected cells and contained many newly formed multivesicular body (MVB)-like compartments that included small vesicles. These MVBs surrounded the Golgi apparatus. Mature virions were found in the MVBs and MVB fusion with plasma membrane, and the release of mature virions together with small vesicles was observed at the cell surface. Immunoelectron microscopy demonstrated that the MVBs contained CD63, an MVB/late endosome marker, and HHV-6 envelope glycoproteins. The viral glycoproteins also localized to internal vesicles in the MVBs and to secreted vesicles (exosomes). Furthermore, we found virus budding at TGN-associated membranes, which expressed CD63, adaptor protein (AP-1) and TGN46, and CD63 incorporation into virions. Our findings suggest that mature HHV-6 virions are released together with internal vesicles through MVBs by the cellular exosomal pathway. This scenario has significant implications for understanding HHV-6's maturation pathway.
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real time pcr determination of Human Herpesvirus 6 antiviral drug susceptibility
Journal of Virological Methods, 2007Co-Authors: Yuji Isegawa, KOICHI YAMANISHI, Masaya Takemoto, Atsushi Ohshima, Nakaba SugimotoAbstract:Abstract A quantitative real-time PCR assay was developed to determine the antiviral drug susceptibility of Human Herpesvirus 6 (HHV-6). After short-term culture of the virus, HHV-6 isolates’ susceptibility to the antiviral ganciclovir (GCV) was determined by measuring the HHV-6 variant B (HHV-6B) DNA levels in culture supernatants and infected cells using real-time PCR. A total of 12 well-characterized GCV-sensitive or -resistant strains and clinical isolates were used. This new assay with real-time PCR readout permitted the rapid (3 days), objective, and reproducible determination of HHV-6 drug susceptibilities with no need for stringent control of the initial multiplicity of infection. Furthermore, the real-time PCR assay results showed good correlation ( r s = 0.95) with those from the conventional TCID 50 (50% tissue culture infecting dose) reduction assay (TRA). Thus, the real-time PCR assay described in this report was found to be a suitable quantitative method for determining the susceptibility of HHV-6 to antiviral drugs. It is faster and simpler than the TRA, and it is amenable to use in the routine diagnostic virology laboratory.
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Human Herpesvirus 6 immediate early 2 protein interacts with heterogeneous ribonucleoprotein k and casein kinase 2
Microbiology and Immunology, 2004Co-Authors: Kazuya Shimada, Kazuhiro Kondo, KOICHI YAMANISHIAbstract:Human Herpesvirus 6 (HHV-6) immediate-early (IE) 2 protein (IE2) may play important but incompletely defined roles during infection. We used yeast two-hybrid screening to detect proteins interacting with HHV-6 IE2, and found heterogeneous nuclear ribonucleoprotein K (hnRNP K) and the beta subunit of casein kinase 2 (CK2beta) specifically interacted with HHV-6 IE2. The interactions were confirmed by GST pull-down assay, coimmunoprecipitation, and colocalization studies. These findings indicate that the HHV-6 IE2 protein interacts with hnRNP K and CK2, and these interactions may affect viral and cellular RNA transcription and translation in viral replication.
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Human Herpesvirus 6 Variant A Glycoprotein H-Glycoprotein L-Glycoprotein Q Complex Associates with Human CD46
Journal of Virology, 2003Co-Authors: Yasuko Mori, Toshiomi Okuno, Xuwei Yang, Pilailuk Akkapaiboon, KOICHI YAMANISHIAbstract:Human CD46 is a cellular receptor for Human Herpesvirus 6 (HHV-6). Virus entry into host cells requires a glycoprotein H (gH)-glycoprotein L (gL) complex. We show that the CD46 ectodomain blocked HHV-6 infection and bound a complex of gH-gL and the 80-kDa U100 gene product, designated glycoprotein Q, indicating that the complex is a viral ligand for CD46.
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Human Herpesvirus 6 variant a but not variant b induces fusion from without in a variety of Human cells through a Human Herpesvirus 6 entry receptor cd46
Journal of Virology, 2002Co-Authors: Yasuko Mori, Pilailuk Akkapaiboon, Tsukasa Seya, Hong Lan Huang, Panadda Dhepakson, KOICHI YAMANISHIAbstract:Human Herpesvirus 6 (HHV-6) is a lymphotropic betaHerpesvirus that productively infects T cells and monocytes. HHV-6 isolates can be differentiated into two groups, variants A and B (HHV-6A and HHV-6B). Here, we show a functional difference between HHV-6A and -6B in that HHV-6A induced syncytium formation of diverse Human cells but HHV-6B did not. The syncytium formation induced by HHV-6A was observed 2 h after infection; moreover, it was found in the presence of cycloheximide, indicating that HHV-6A induced fusion from without (FFWO) in the target cells. Furthermore, the fusion event was dependent on the expression of the HHV-6 entry receptor, CD46, on the target cell membrane. In addition, we determined that short consensus repeat 2 (SCR2), -3, and -4 of the CD46 ectodomain were essential for the formation of the virus-induced syncytia. Monoclonal antibodies against glycoproteins B and H of HHV-6A inhibited the fusion event, indicating that the syncytium formation induced by HHV-6A required glycoproteins H and B. These findings suggest that FFWO, which HHV-6A induced in a variety of cell lines, may play an important role in the pathogenesis of HHV-6A, not only in lymphocytes but also in various tissues, because CD46 is expressed ubiquitously in Human tissues.
Danielle M. Zerr - One of the best experts on this subject based on the ideXlab platform.
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efficient identification of inherited chromosomally integrated Human Herpesvirus 6 using specimen pooling
Journal of Clinical Virology, 2016Co-Authors: Meei Li Huang, Danielle M. Zerr, Joshua A Hill, Amalia Magaret, Keith R Jerome, Ruth HallsedlakAbstract:Abstract Background Human Herpesvirus 6 (HHV-6) has a unique ability to integrate into chromosomal telomeres. Vertical transmission via germ cell integration results in offspring with inherited chromosomally integrated (ci)HHV-6 in all nucleated cells, affecting ∼1% of the population. Objectives Inherited ciHHV-6 may be a direct or indirect mediator of Human disease, but efficient identification of affected individuals is a fundamental roadblock to larger studies exploring the clinical importance of this condition. Study design A group testing strategy was designed to efficiently identify individuals with inherited ciHHV-6. DNA was extracted from 2496 cellular samples from hematopoietic cell transplant (HCT) donor–recipient pairs. Pools of 12 samples were screened for HHV-6 DNA with quantitative (q)PCR. Individual samples from high positive pools were tested with qPCR, and high positive individual samples were tested for inherited ciHHV-6 using droplet digital (dd)PCR to determine HHV-6 DNA copies/cellular genome. Results Thirty-one pools had high positive HHV-6 DNA detection with >10 3 HHV-6 DNA copies/μg. Each pool had one sample with >10 4 copies/μg HHV-6 DNA. Inherited ciHHV-6 was confirmed by ddPCR in every high positive sample (>10 3 HHV-6 DNA copies/μg), yielding a prevalence of 1.5% in HCT recipients and 0.96% in donors. We performed 580 qPCR tests to screen 2496 samples for inherited ciHHV-6, a 77% reduction in testing. Conclusions Inherited ciHHV-6 can be efficiently identified by specimen pooling coupled with modern molecular techniques. This algorithm can be used to facilitate cost-effective identification of patients with inherited ciHHV-6, thereby removing a major hurdle for large-scale study of its clinical impact.
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identification of chromosomally integrated Human Herpesvirus 6 by droplet digital pcr
Clinical Chemistry, 2014Co-Authors: Ruth Hall Sedlak, Meei Li Huang, Danielle M. Zerr, Linda S Cook, Amalia Magaret, Michael Boeckh, Keith R JeromeAbstract:BACKGROUND: Human Herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests. METHODS: A droplet digital PCR (ddPCR) assay was developed to identify ciHHV-6 in cellular patient samples by precisely determining the ratio of HHV-6 to cellular DNA. We validated the assay on confirmed ciHHV-6 patient samples and a cell line derived from a ciHHV-6 patient, and we analyzed hematopoietic stem cell transplant patients suspected of having ciHHV-6. We additionally evaluated whether the assay could be applied to stored plasma samples from a study of clinical correlates of HHV-6. RESULTS: The ddPCR assay accurately identified ciHHV-6 in cellular samples (buffy coat, peripheral blood mononuclear cells), giving a ratio very close to 1 HHV-6/cell [mean (SD), 1.02 (0.03)] in fluorescence in situ hybridization–confirmed sample). In stored plasma samples, the assay performance was set by design to have 100% sensitivity, which resulted in 82% specificity for ciHHV-6. CONCLUSIONS: The possibility of ciHHV-6 is often overlooked in patients with detectable HHV-6 viral loads by quantitative PCR. Our ddPCR test provides rapid and accurate laboratory identification of ciHHV-6 from easily obtained cellular samples. In addition, the assay provides excellent sensitivity and specificity using stored plasma samples, facilitating retrospective analysis of the clinical significance of ciHHV-6.
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Human Herpesvirus 6 and central nervous system disease in hematopoietic cell transplantation
Journal of Clinical Virology, 2006Co-Authors: Danielle M. ZerrAbstract:Human Herpesvirus 6 infects virtually all children within the first few years of life and like other Herpesviruses, establishes latency after primary infection. In immunocompromised hosts, especially hematopoietic cell transplant (HCT) recipients, HHV-6 has been demonstrated to reactivate frequently. This reactivation has been associated with a number of different clinical endpoints in HCT recipients, including central nervous system (CNS) disease. There have been many detailed descriptions of individual patients with HHV-6-associated encephalitis. In addition, longitudinal observational studies have established a correlation between systemic HHV-6 reactivation and CNS dysfunction. Further research is needed to define optimal diagnostic, prevention, and treatment strategies.
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clinical outcomes of Human Herpesvirus 6 reactivation after hematopoietic stem cell transplantation
Clinical Infectious Diseases, 2005Co-Authors: Danielle M. Zerr, Meei Li Huang, Lawrence Corey, Michael Boeckh, Hyung W Kim, Long NguyAbstract:Background Although Human Herpesvirus 6 (HHV-6) is known to reactivate during hematopoietic stem cell transplantation (HSCT), the clinical significance of this finding is controversial. Methods We used a quantitative PCR test for HHV-6 to assay plasma samples prospectively collected from a cohort of 110 allogeneic HSCT recipients to evaluate the clinical effects of HHV-6 infection. A retrospective review of medical records was performed to determine clinical end points. Results HHV-6 reactivation occurred in 52 (47%) of the 110 subjects. Factors that increased the risk of subsequent HHV-6 reactivation were hematologic malignancy that occurred at a time other than the first remission (adjusted P = .002), a mismatch in the sexes of donor and recipient (adjusted P=.05), younger age (adjusted P = .01), and the receipt of glucocorticoids (adjusted P = .06). HHV-6 reactivation was associated with subsequent all-cause mortality (adjusted hazard ration [HR], 2.9; 95% confidence interval [CI], 1.1-7.5), grade 3-4 graft-versus-host disease (GVHD) (adjusted HR, 4.9; 95% CI, 1.5-16), a lower probability of monocyte engraftment (adjusted HR, 0.42; 95% CI; 0.22-0.80), a lower probability of platelet engraftment (adjusted HR, 0.47; 95% CI, 0.21-1.1; P = .05) and a higher platelet transfusion requirement (adjusted P = .02). A higher level of HHV-6 DNA was associated with subsequent central nervous system (CNS) dysfunction (HR, 21; 95% CI, 1.8-249). Conclusions HHV-6 reactivation is common after allogeneic HSCT and is associated with subsequent delayed monocyte and platelet engraftment, increased platelet transfusion requirements, all-cause mortality, grade 3-4 GVHD, and CNS dysfunction.
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primary Human Herpesvirus 6 associated with an afebrile seizure in a 3 week old infant
Journal of Medical Virology, 2002Co-Authors: Danielle M. Zerr, Meei Li Huang, Lawrence Corey, Laurence C Yeung, Rose Mary Obrigewitch, Lisa M FrenkelAbstract:We describe a 3-week-old male infant with an afebrile seizure in whom serologic and polymerase chain reaction (PCR) findings support concomitant primary Human Herpesvirus 6 (HHV-6) infection. Although HHV-6 infection has been associated with first-time febrile seizures and encephalitis in both immunocompetent and immunocompromised hosts, it has not been associated previously with afebrile seizures in healthy infants. This report provides additional evidence of the neuropathogenic potential of HHV-6.
Lawrence Corey - One of the best experts on this subject based on the ideXlab platform.
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clinical outcomes of Human Herpesvirus 6 reactivation after hematopoietic stem cell transplantation
Clinical Infectious Diseases, 2005Co-Authors: Danielle M. Zerr, Meei Li Huang, Lawrence Corey, Michael Boeckh, Hyung W Kim, Long NguyAbstract:Background Although Human Herpesvirus 6 (HHV-6) is known to reactivate during hematopoietic stem cell transplantation (HSCT), the clinical significance of this finding is controversial. Methods We used a quantitative PCR test for HHV-6 to assay plasma samples prospectively collected from a cohort of 110 allogeneic HSCT recipients to evaluate the clinical effects of HHV-6 infection. A retrospective review of medical records was performed to determine clinical end points. Results HHV-6 reactivation occurred in 52 (47%) of the 110 subjects. Factors that increased the risk of subsequent HHV-6 reactivation were hematologic malignancy that occurred at a time other than the first remission (adjusted P = .002), a mismatch in the sexes of donor and recipient (adjusted P=.05), younger age (adjusted P = .01), and the receipt of glucocorticoids (adjusted P = .06). HHV-6 reactivation was associated with subsequent all-cause mortality (adjusted hazard ration [HR], 2.9; 95% confidence interval [CI], 1.1-7.5), grade 3-4 graft-versus-host disease (GVHD) (adjusted HR, 4.9; 95% CI, 1.5-16), a lower probability of monocyte engraftment (adjusted HR, 0.42; 95% CI; 0.22-0.80), a lower probability of platelet engraftment (adjusted HR, 0.47; 95% CI, 0.21-1.1; P = .05) and a higher platelet transfusion requirement (adjusted P = .02). A higher level of HHV-6 DNA was associated with subsequent central nervous system (CNS) dysfunction (HR, 21; 95% CI, 1.8-249). Conclusions HHV-6 reactivation is common after allogeneic HSCT and is associated with subsequent delayed monocyte and platelet engraftment, increased platelet transfusion requirements, all-cause mortality, grade 3-4 GVHD, and CNS dysfunction.
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primary Human Herpesvirus 6 associated with an afebrile seizure in a 3 week old infant
Journal of Medical Virology, 2002Co-Authors: Danielle M. Zerr, Meei Li Huang, Lawrence Corey, Laurence C Yeung, Rose Mary Obrigewitch, Lisa M FrenkelAbstract:We describe a 3-week-old male infant with an afebrile seizure in whom serologic and polymerase chain reaction (PCR) findings support concomitant primary Human Herpesvirus 6 (HHV-6) infection. Although HHV-6 infection has been associated with first-time febrile seizures and encephalitis in both immunocompetent and immunocompromised hosts, it has not been associated previously with afebrile seizures in healthy infants. This report provides additional evidence of the neuropathogenic potential of HHV-6.
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effect of antivirals on Human Herpesvirus 6 replication in hematopoietic stem cell transplant recipients
Clinical Infectious Diseases, 2002Co-Authors: Danielle M. Zerr, Rachel A Carter, Meei Li Huang, Lawrence Corey, Deepti GuptaAbstract:Human Herpesvirus 6 (HHV-6) appears to cause central nervous system (CNS) syndromes, especially in hematopoietic stem cell transplant (HSCT) recipients. We reviewed our experience with HHV-6-associated CNS disease to evaluate both the clinical and virological presentation and response to antiviral therapy. A search of our virology database from January 1998 through June 2000 identified 11 HSCT recipients who had HHV-6 DNA detected by polymerase chain reaction in cerebrospinal fluid (CSF); 8 of whom had CNS dysfunction without another clear etiology identified. HHV-6 levels in serum and CSF were evaluated before and after ganciclovir and/or foscarnet therapy. Median log HHV-6 CSF levels appeared to decrease over time concurrent with antiviral therapy (serum level, 2.0 vs. 0 copies/mL [P = .38]; CSF level, 4.4 vs. 2.0 copies/mL [P = .13], sign test). Our data suggests that HHV-6 may cause moderate to severe CNS disease after HSC transplantation. Prospective studies are needed to define the spectrum of HHV-6-associated disease and to determine whether antiviral therapy offers clinical benefit.
Louis Flamand - One of the best experts on this subject based on the ideXlab platform.
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chromosomally integrated Human Herpesvirus 6 questions and answers
Reviews in Medical Virology, 2012Co-Authors: Philip E. Pellett, Mary T Caserta, Caroline B Hall, Vincent Descamps, Louis Flamand, Agnes Gautheretdejean, Henri Agut, Dharam V Ablashi, Peter F Ambros, Rammurti T KambleAbstract:Chromosomally integrated Human Herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease. Copyright © 2011 John Wiley & Sons, Ltd.
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mapping of Human Herpesvirus 6 immediate early 2 protein transactivation domains
Virology, 2006Co-Authors: Andru Tomoiu, Annie Gravel, Louis FlamandAbstract:The immediate-early 2 (IE2) protein of Human Herpesvirus 6 (HHV-6) is a potent transactivator of multiple cellular and viral promoters. Deletion mutants of HHV-6 variant A IE2 allowed us to map functional transactivation domains acting on complex and minimal promoter sequences. This mapping showed that both the N-terminal and C-terminal domains of IE2 are required for efficient transactivation, and that deletion of the C-terminal (1397-1466) tail of IE2 drastically reduces both transactivation and the intranuclear distribution of IE2. Moreover, we determined that the ATF/CRE binding site within the HHV-6A polymerase promoter is not required for efficient transactivation by IE2, whereas the R3 repeat region of the putative immediate-early promoter of HHV-6A is responsive to and positively regulated by IE2. These results contrast sharply to that of Human cytomegalovirus (HCMV) IE2, which down-regulates its promoter. Our characterization of HHV-6 IE2 transactivating activity provides a better understanding of the complex interactions of this protein with the viral and cellular transcription machinery and highlights significant differences with the IE2 protein of HCMV.
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generation and characterization of a monoclonal antibody specific for Human Herpesvirus 6 variant a immediate early 2 protein
Journal of Clinical Virology, 2003Co-Authors: Suzie Arsenault, Annie Gravel, Jean Gosselin, Louis FlamandAbstract:Two variants (A and B) of Human Herpesvirus 6 (HHV-6) can be isolated from Humans, with each variant having unique biological properties. HHV-6 variant typing is mainly done following amplification of viral genomic DNA followed by restriction endonuclease digestion. Our objective was to generate a monoclonal antibody (mAb) that would allow us to discriminate between variants A and B of HHV-6. BALB/c mice were immunized with a recombinant glutathione-S-transferase protein fused to the immediate � /early (IE) 2 protein from HHV-6 variant A. Following splenocytes fusion, one IgG1 k light chain mAb (P6H8) was isolated and found to react specifically with variant A IE2 protein in immunofluorescence and western blot assays. The P6H8 antibody represents a useful tool for both fundamental research and clinical applications allowing for the discrimination of infections caused by HHV-6 variants Ao r B. # 2003 Elsevier Science B.V. All rights reserved.
Michael Boeckh - One of the best experts on this subject based on the ideXlab platform.
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identification of chromosomally integrated Human Herpesvirus 6 by droplet digital pcr
Clinical Chemistry, 2014Co-Authors: Ruth Hall Sedlak, Meei Li Huang, Danielle M. Zerr, Linda S Cook, Amalia Magaret, Michael Boeckh, Keith R JeromeAbstract:BACKGROUND: Human Herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests. METHODS: A droplet digital PCR (ddPCR) assay was developed to identify ciHHV-6 in cellular patient samples by precisely determining the ratio of HHV-6 to cellular DNA. We validated the assay on confirmed ciHHV-6 patient samples and a cell line derived from a ciHHV-6 patient, and we analyzed hematopoietic stem cell transplant patients suspected of having ciHHV-6. We additionally evaluated whether the assay could be applied to stored plasma samples from a study of clinical correlates of HHV-6. RESULTS: The ddPCR assay accurately identified ciHHV-6 in cellular samples (buffy coat, peripheral blood mononuclear cells), giving a ratio very close to 1 HHV-6/cell [mean (SD), 1.02 (0.03)] in fluorescence in situ hybridization–confirmed sample). In stored plasma samples, the assay performance was set by design to have 100% sensitivity, which resulted in 82% specificity for ciHHV-6. CONCLUSIONS: The possibility of ciHHV-6 is often overlooked in patients with detectable HHV-6 viral loads by quantitative PCR. Our ddPCR test provides rapid and accurate laboratory identification of ciHHV-6 from easily obtained cellular samples. In addition, the assay provides excellent sensitivity and specificity using stored plasma samples, facilitating retrospective analysis of the clinical significance of ciHHV-6.
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clinical outcomes of Human Herpesvirus 6 reactivation after hematopoietic stem cell transplantation
Clinical Infectious Diseases, 2005Co-Authors: Danielle M. Zerr, Meei Li Huang, Lawrence Corey, Michael Boeckh, Hyung W Kim, Long NguyAbstract:Background Although Human Herpesvirus 6 (HHV-6) is known to reactivate during hematopoietic stem cell transplantation (HSCT), the clinical significance of this finding is controversial. Methods We used a quantitative PCR test for HHV-6 to assay plasma samples prospectively collected from a cohort of 110 allogeneic HSCT recipients to evaluate the clinical effects of HHV-6 infection. A retrospective review of medical records was performed to determine clinical end points. Results HHV-6 reactivation occurred in 52 (47%) of the 110 subjects. Factors that increased the risk of subsequent HHV-6 reactivation were hematologic malignancy that occurred at a time other than the first remission (adjusted P = .002), a mismatch in the sexes of donor and recipient (adjusted P=.05), younger age (adjusted P = .01), and the receipt of glucocorticoids (adjusted P = .06). HHV-6 reactivation was associated with subsequent all-cause mortality (adjusted hazard ration [HR], 2.9; 95% confidence interval [CI], 1.1-7.5), grade 3-4 graft-versus-host disease (GVHD) (adjusted HR, 4.9; 95% CI, 1.5-16), a lower probability of monocyte engraftment (adjusted HR, 0.42; 95% CI; 0.22-0.80), a lower probability of platelet engraftment (adjusted HR, 0.47; 95% CI, 0.21-1.1; P = .05) and a higher platelet transfusion requirement (adjusted P = .02). A higher level of HHV-6 DNA was associated with subsequent central nervous system (CNS) dysfunction (HR, 21; 95% CI, 1.8-249). Conclusions HHV-6 reactivation is common after allogeneic HSCT and is associated with subsequent delayed monocyte and platelet engraftment, increased platelet transfusion requirements, all-cause mortality, grade 3-4 GVHD, and CNS dysfunction.