OBJECTIVETo study the potential relationship between HHV-6 activation and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HSCT).

METHODSPeripheral blood samples were collected before and weekly after HSCT from 72 consecutive recipients. HHV-6 DNAemia was monitored by nested polymerase chain reaction (PCR). The genotypes of HHV-6 were identified by Hind III restriction assay.

RESULTSOf the 72 patients, HHV-6 DNAemia were detected in 45 (62.5%) on a median of day 14 (range, 7 - 63 days) after HSCT. Grade I - IV aGHVD occurred in 40 (55.6%) on a median of day 26 (range, 9 -73 days). The median onset time of HHV-6 DNAemia was significantly earlier than that of aGHVD (P = 0.018). Compared with that in HHV-6 DNAemia negative [HHV-6(-)] patients, the cumulative incidence of grade I - IV aGHVD was higher (68.9% vs. 33.3% , P = 0.003) in HHV-6 (+) patients. Cumulative incidence of grade II - IV aGVHD in HHV-6 (+) cohort was also higher than that in HHV-6 (-) cohort (35.6% vs 14.8% , P = 0.027). Cumulative incidence of grade I - IV aGVHD was higher in patients with both HHV-6 and CMV positive (CMV+/HHV-6+) than in those with either CMV (CMV+/HHV-6-) or HHV-6 positive (CMV+/HHV-6+) and neither of them positive (CMV-/HHV-6-) [78.9% (30/38), 55. 6% (5/9) , 14. 3% (1/7) and 22. 2% (4/18), respectively, P = 0. 0001]. Cumulative incidence of grade II - IV aGVHD in CMV+/HHV-6+ group was also higher than that in CMV+/HHV-6-, CMV-/HHV-6+ and CMV-/HHV-6- groups [42.1% (16/38), 22.2% (2/9), 0% (0/7) and 11.1% (2/18), P = 0. 008].

CONCLUSIONSPatients with HHV-6 activation or HHV-6/CMV co-infection maybe involved in the occurrence of aGVHD after HSCT.

Cytomegalovirus ; genetics ; isolation & purification ; Genes, Viral ; Graft vs Host Disease ; etiology ; virology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Herpesvirus 6, Human ; genetics ; physiology ; Humans ; Polymerase Chain Reaction ; methods ; Postoperative Complications ; etiology ; virology ; Roseolovirus Infections ; etiology

In order to study the prevalence of human herpesvirus 6 (HHV-6) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients in China and to analyze the relationship between HHV-6 and cytomegalovirus (CMV) infection in post-HSCT patients, nested polymerase chain reaction (PCR) was used to monitor HHV-6 DNAemia in 72 consecutive allo-HSCT recipients. 680 EDTA anticoagulated peripheral blood specimens were gathered before HSCT or weekly until 12 weeks after allo-HSCT. The variants of HHV-6 were identified by Hind III restriction analysis. CMV-pp65 antigenemia was detected by immunofluorescence stain. The results showed that HHV-6 DNAemia was detected at least once in 62.5% (45/72) of the patients on the median day 14 (range, 7 - 63 days) after allo-HSCT, and HHV-6B was the predominant variant. CMV antigenemia was detected at least once in 65.3% (47/72) of the patients on the median day 43 (range, 14 - 105 days) after allo-HSCT. Co-infection of HHV-6 and CMV (HHV-6+/CMV+) occurred in 52.8% (38/72) recipients. The onset of HHV-6 DNAemia was earlier than that of CMV antigenemia (P < 0.0001). Patients with HHV-6 DNAemia positive were more likely to have concurrent CMV antigenemia than HHV-6 DNAemia negative patients (84.4% vs 33.3%, P = 0.0001) after allo-HSCT. Among the herpesvirus related disease, the relatively high incidence of hemorrhage cystitis (HC) occurred in 23.6% (17/72) of post-HSCT patients. 88.2% (15/17) of HC developed in HHV-6 positive patients, and 82.3% (14/17) occurred in CMV+/HHV-6+ patients. It is concluded that infection of HHV-6, co-infection of HHV-6 and CMV, commonly occurred in post-HSCT patients in China, HHV-6 infection closely related to CMV antigenemia.
Adolescent ; Adult ; Child ; China ; epidemiology ; Cytomegalovirus ; genetics ; isolation & purification ; Cytomegalovirus Infections ; complications ; epidemiology ; DNA, Viral ; blood ; genetics ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Herpesvirus 6, Human ; isolation & purification ; physiology ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prevalence ; Roseolovirus Infections ; complications ; epidemiology ; virology

Anti-Bacterial Agents ; therapeutic use ; Antigens, CD20 ; metabolism ; CD3 Complex ; metabolism ; CD4 Antigens ; metabolism ; Fever ; drug therapy ; virology ; Herpesvirus 6, Human ; isolation & purification ; Humans ; Lymph Nodes ; pathology ; virology ; Lymphadenitis ; drug therapy ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Roseolovirus Infections ; drug therapy ; metabolism ; virology

OBJECTIVETo establish fluorescent quantitative PCR method for detecting human herpes virus type 6 (HHV6).

METHODSAccording to the specific sequence of human herpes virus type 6 genes, the primers and the fluorescent probe (TaqMan) were designed and synthesized. The fragment generated from HHV 6 gene as template was cloned into the pMD18-T vector which was constructed from the pUC 18. And the positive recombinant plasmid was 1:10 diluted and used as standard quantitative template to make the standard curve for sample detection.

RESULTSThe standard curve indicated the linear relationship between Ct (cycle threshold) and template concentration. The clinical samples from 135 cases were detected by this system, 16 cases among 135 were positive.

CONCLUSIONThe fluorescent quantitative PCR method for the detection of human herpes virus type 6 is simple and accurate, and this method may be helpful to clinical diagnosis.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; DNA Primers ; DNA Probes ; DNA, Viral ; genetics ; Female ; Herpesvirus 6, Human ; genetics ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Purpura, Thrombocytopenic, Idiopathic ; diagnosis ; virology ; Reproducibility of Results ; Roseolovirus Infections ; diagnosis ; virology ; Sensitivity and Specificity ; Young Adult

This study examined the anti-viral effect of ursolic acid on guinea pig cytomegalovirus (GPCMV) and explored the steps of viral replication targeted by ursolic acid. Cytopathic effect assay and MTT method were employed to determine the 50% cellular cytotoxicity (CC(50)), 50% effective concentration (EC(50)) and therapeutic index (TI) with GPCMV. To investigate the specific anti-viral effect of ursolic acid at different temperatures and time points, two other medicines, ganciclovir and Jinyebaidu (JYBD), serving as controls, were studied for comparison. Our results showed that the CC50 of ganciclovir, JYBD and ursolic acid were 333.8, 3015.6, 86.7 μg/mL, respectively; EC(50) of ganciclovir, JYBD and ursolic acid was 48.1, 325.5 and 6.8 μg/mL, respectively; TI of ganciclovir, JYBD and ursolic acid was 7, 9, 13, respectively. Similar with ganciclovir, ursolic acid could inhibit the viral synthesis, but did not affect the viral adsorption onto and penetration into cells. We are led to conclude that the anti-cytomegalovirus effect of ursolic acid is significantly stronger than ganciclovir or JYBD, and the cytotoxic effect of ursolic acid lies in its ability to inhibit viral synthesis.
Animals ; Antiviral Agents ; pharmacology ; Cells, Cultured ; Guinea Pigs ; Roseolovirus ; drug effects ; Triterpenes ; pharmacology

BACKGROUND: Pityriasis rosea is a common, acute self-limiting papulosquamous disorder in which many studies suggest viral causative factors in its pathogenesis. Recently, the link between pityriasis rosea and the reactivation of human herpes virus-6 (HHV-6) and HHV-7 infection has been suggested. This evidence suggests that targetting HHV-6 or HHV-7 may be an effective treatment for pityriasis rosea. OBJECTIVE: We treated pityriasis rosea patients with oral famciclovir to investigate the effect of oral famciclovir in pityriasis rosea. METHODS: A case group of seventeen patients with pityriasis rosea were treated with oral famciclovir (250 mg 3 times daily for 7 days). Clinical evaluation at 0, 1 & 2 weeks was undertaken. A skin biopsy and polymerase chain reaction analysis of HHV-6 from a skin specimen were performed. We analyzed 19 patients with pityriasis rosea who were treated with topical steroid and oral antihistamines retrospectively and considered them as the control group. RESULTS: On the 7th day after oral famciclovir treatment was started, pityriasis rosea had regressed completely in 3 patients (17.6%) and had regressed partially in 9 patients (52.9%). On the 14th day, 12 patients (70.6%) had achieved more than partial regression. On the 7th day, systemic symptoms had improved in all 9 patients. Clearance of skin lesions was achieved in average 7.57 days in patients who had regressed completely after 14 days' treatment. Histological examination of patients was compatible with pityriasis rosea and polymerase chain reaction analysis of HHV-6 was negative in all 8 patients. Compared with the control group, the treatment for patients in the case group seemed to have better effects, but statistical analysis failed to show any significant differences between the two groups. CONCLUSION: Famciclovir was not effective in the treatment of pityriasis rosea, but further investigation is needed.
Biopsy ; Herpesvirus 6, Human ; Herpesvirus 7, Human ; Histamine Antagonists ; Humans ; Pityriasis Rosea* ; Pityriasis* ; Polymerase Chain Reaction ; Retrospective Studies ; Skin ; Skin Diseases, Papulosquamous

OBJECTIVE: To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival. METHODS: Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated. RESULTS: Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05). CONCLUSION IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Cytokines/metabolism* ; Epstein-Barr Virus Infections/complications* ; Interleukin-6 ; Clinical Relevance ; Interleukin-7 ; Interleukin-8 ; Interleukin-9 ; Chemokines ; Interferons

Castleman's disease (CD) is a rare lymphoproliferative disorder that comprises at least two distinct clinical subtypes (unicentric and multicentric). Three pathologic variants (hyaline vascular variant, plasma cell variant, and mixed variant) have been recognized. In addition to interleukin-6 and human herpes virus 8, some other cytokines and viruses may also be involved in the pathogenesis of CD. This review summarizes the recent advances in the underlying pathogenesis of CD, with an attempt to provide evidence for new treatment options that may change the current treatment strategies and improve patients' outcomes.
Castleman Disease ; Herpesvirus 8, Human ; Humans ; Interleukin-6

No abstract available.
Herpesviridae* ; Herpesvirus 7, Human ; Herpesvirus 8, Human ; Humans*

J6-1 cell line is the first leukemic cell line established in China. It is a multi-clone cell line infected with both EBV and HHV-6. Many cytokines, receptors and other genes were cloned from J6-1 cell line since its establishment 30 years ago. Valuable information on leukemic characteristics and functions were obtained from the studies on this cell line, which could be categorized into several research subjects. These achievements implied the unique research value of multi-clone cell lines. This comment focuses attention on research advance of the J6-1 leukemic cell line in 30 years, including heterogeneity and multi-cloning of J6-1 cells, survival mechanism of J6-1 cell populations, abnormal intercellalar communication of J6-1 cells with its significance and inspiration from J6-1 cell line.
Cell Line, Tumor ; Cell Transformation, Neoplastic ; Clone Cells ; Herpesvirus 4, Human ; immunology ; Herpesvirus 6, Human ; immunology ; Humans ; Leukemia ; pathology