Cytomegalovirus,human herpesvirus-6, and human herpesvirus-7 in hematological patients

The prototype member of the Betaherpesvirinae subfamily, cytomegalovirus (CMV), is the most important infectious pathogen in transplant recipients, including those receiving bone marrow or stem cell grafts. Overt CMV disease such as pneumonitis is notoriously difficult to treat. Antiviral prophylaxis, rapid diagnostic tests to identify CMV infection, and preemptive antiviral chemotherapy are significant improvements in the management of CMV. As the kinetics of the immune response to CMV become better defined, immunotherapeutic approaches should be introduced to complement current management strategies. Two newly identified betaherpesviruses, human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7), are genetically more closely related to each other than to CMV. Both are highly prevalent in the general population and infections post-bone marrow transplantation are common. These viruses are not as pathogenic as CMV but HHV-6 at least can cause disease such as encephalitis, hepatitis, and bone marrow suppression. Both of these newer herpesviruses are potentially susceptible to existing and licensed antiherpesvirus drugs.     

Prevalence of human cytomegalovirus (HCMV) gB genotypes in Thai patients

Human cytomegalovirus (HCMV) infection can cause asymptomatic to symptomic diseases leading to morbidity and mortality especially in immunocompromized patients. One factor of the difference in clinical outcome is the distinction of HCMV strain. As HCMV glycoprotein (g)B plays an important role in viral entry and neutralizing antibody induction, HCMV gB genotypes were determined in 161 clinical specimens containing HCMV-DNA obtained from patients at King Chulalongkorn Memorial Hospital, Bangkok, Thailand during the year 2000 and 2004. Of the 113 (70%) samples that were able to be genotyped, mixed gB genotype was demonstrated in 35%, followed by gB1 (33%), gB3 (15%), gB2 (11%), and untyped (7%); gB4 was not detected. The distribution of HCMV gB genotypes between genders was not significantly different. Mixed gB genotype (35%) was found in HIV- infected patients.     

Prevalence of blood-borne viral infections (cytomegalovirus, human herpesvirus-6, human herpesvirus-7, human herpesvirus-8, human T-cell lymphotropic virus-I/II, human retrovirus-5) among blood donors in Latvia

The identification of blood-borne viral infections is important in transfusion medicine. The aim of this study was to evaluate the prevalence of human herpesvirus (HHV) [cytomegalovirus (CMV), HHV-6, HHV-7 HHV-8] and human retrovirus (HRV) (human T-cell lymphotropic virus (HTLV)-I/II, HRV-5) infections among apparently healthy Latvian blood donors. DNA extracted from peripheral blood leukocytes (PBL) of 150 individuals was tested for herpesviruses by sensitive polymerase chain reaction (PCR) technique. None of the blood donors was positive for HHV-8 infection, while the incidence of latent beta-herpesvirus infections was high: single infection by CMV, HHV-6, and HHV-7 was detected in 2.6%, 8.0%, and 43.3% of blood donors, respectively. Simultaneous dual and triple infections of these viruses were observed in 28.0% and 4.7% of individuals, respectively. Active infection by CMV and HHV-6 was not found, but HHV-7 DNA was present in plasma of 10.6% of the blood donors. While all blood donors were HTLV-II and HRV-5 negative, 4.6% of HTLV-I seronegative blood donors were positive for the HTLV-I tax gene, although none of them harbored sequences for structural genes of the provirus. Based on our results, we conclude that monitoring of beta-herpesvirus infections in blood donors can be important in cases of transfusions to immunocompromised persons. HHV-8, as well as the retroviruses HTLV-II and HRV-5, were not found in blood of Latvian blood donors. More investigations are required to explain the presence of the HTLV-I tax sequence in seronegative blood donors.     

Endothelial damage caused by cytomegalovirus and human herpesvirus-6

Infection with cytomegalovirus (CMV) or human herpesvirus-6 (HHV-6) may have a role in vascular endothelial damage after bone marrow transplantation (BMT). In total, 41 patients who underwent BMT were classified into four groups (12, 10, 7, and 12 patients who were infected with both CMV and HHV-6, CMV alone, HHV-6, and neither virus, respectively). Levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were 7.5+/-1.7 FU/ml, 76.4+/-24.1 ng/ml, and 9.51+/-1.1 pmol/ml, respectively, in the patients with both viruses, while the respective values were 2.9+/-0.67 FU/ml, 33.8+/-8.09 ng/ml, and 2.90+/-1.4 pmol/ml in patients infected with CMV alone, 4.8+/-0.96 FU/ml, 47.7+/-9.21 ng/ml, and 5.48+/-0.55 pmol/ml in patients with HHV-6 alone, and 1.6+/-0.39, 17.5+/-7.88 ng/ml, and 0.45+/-0.3 in those with neither virus. All three markers were significantly higher in the three groups with at least one virus than in the uninfected patients (P<0.05), and were also higher in patients with HHV-6 alone than in those with CMV alone (P<0.05). These results suggest that infection by CMV or HHV-6 causes vascular endothelial injury, with HHV-6 having a stronger effect than CMV, and combined infection having a stronger effect than either virus alone. Such viral infection may be a cause of thrombotic microangiopathy after BMT.     

Prevalence of cytomegalovirus antibodies among various age groups of Thai population

The prevalence of CMV antibody in various groups of Thai population was studied. Pregnant women and young children had been infected with CMV more than the other studied groups. Children of both sex had equal chance of getting CMV infection while the risk of CMV infection in adult between male and female was significantly difference (p < 0.001). Pregnant women had higher chance to get CMV infection than normal women. Prevalence of CMV antibody at present was similar to previous studies.     

Comparison between cytomegalovirus hepatitis and Epstein-Barr virus hepatitis in healthy adults

In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein-Barr virus (EBV) hepatitis in previously healthy adults, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed. CMV hepatitis showed a tendency to increase in our department. In comparison with EBV hepatitis, CMV hepatitis occurred in significantly older hosts than EBV hepatitis. We found that lymphadenopathy, cough and sore throat was more common in EBV hepatitis than in CMV hepatitis. The number of peripheral white blood cell count and atypical lymphocytes, and serum GOT, GPT, LDH and CRP levels of CMV and EBV hepatitis showed no significant differences.     

慢性牙周炎龈下HCMV和EBV感染及其混合感染率与牙周病变程度的关系

目的了解慢性牙周炎(CP)龈下标本中人巨细胞病毒(HCMV)、Epstein-Barr病毒(EBV)感染和混合感染率及其与CP病变程度的关系。方法分别以HCMV糖蛋白B(gB)基因和EBV核抗原2(EBNA2)为靶基因,采用套式PCR(nPCR)检测130例CP患者、65例牙龈炎患者和35例牙周健康者共920份龈下标本中的HCMV及EBV-1和EBV-2。以牙龈指数(GI)、牙周附着丧失(AL)和牙周袋深度(PD)为观察指标,了解HCMV和EBV-1或EBV-2感染及其混合感染与CP牙周炎症和牙周破坏程度的关系。结果CP标本HCMV阳性率(63.5%)、EBV-1(27.9%)和EBV-2(9.8%)阳性率均显著高于牙龈炎(49.2%,16.9%,3.1%)和健康牙周标本(40.0%,13.6%,0.07%)。CP标本HCMV和EBV-1(18.5%)、HC-MV和EBV-2(7.5%)混合感染阳性率均显著高于牙龈炎标本(4.2%,0.08%)和健康牙周标本(2.1%,0.07%)。牙龈炎和健康牙周标本上述检测阳性率之间均无统计学差异。EBV-1或EBV-2感染与GI、AL、PD均无关。HCMV感染、HCMV和EBV-1及HCMV和EBV-2混合感染虽与GI均无关,但与AL和PD密切相关。结论HCMV或EBV-1、EBV-2感染可能参与CP发病。HCMV感染与CP牙周破坏中有重要作用,EBV-1与HCMV混合感染时可加重CP病变程度。     

Comparison between sporadic cytomegalovirus hepatitis and Epstein-Barr virus hepatitis in previously healthy adults

Abstract: In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein-Barr virus (EBV) hepatitis, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed in 20 patients with CMV and 11 patients with EBV. While most signs and symptoms of CMV and EBV hepatitis showed no significant differences, we found that cervical lymphadenopathy was more common in EBV hepatitis than in CMV hepatitis (p < 0.01). Frequency of epigastralgia was more common in CMV hepatitis than EBV hepatitis (p<0.05). The percentage of peripheral blood monocytes in the white blood cell count in CMV hepatitis was greater than in EBV hepatitis (p<0.01). Low CD4 levels and high CD8 levels made CD4/CD8 low in peripheral lymphocytes of both groups of hepatitis. Ten EBV hepatitis patients received antibiotics in the early stage of the disease in which two (25%) developed severe erythematous rashes. Four CMV hepatitis patients received antibiotics and did not develop rashes. Identification of early clinical parameters capable of differentiating CMV hepatitis from EBV hepatitis is important.     

Prevalence of cytomegalovirus antibody in subjects between the ages of 6 and 22 years

We determined the prevalence of antibody to cytomegalovirus (CMV) in three groups between 1985 and 1987. Group I consisted of 511 subjects 6-22 y old, group II consisted of 920 subjects 18-21 y old, and group III of 113 subjects 18-22 y old. The overall prevalence of antibody in these three groups was 34%, 24%, and 28%, respectively. Prevalence of antibody in white subjects (24%, 21%, and 24%, respectively) was significantly lower than that in nonwhite subjects. In group I, there was no increase in prevalence with age in white subjects, but the percentage of individuals with antibody increased with age among nonwhite subjects. It is of obvious concern that a large proportion of white women entering childbearing years lack CMV antibody.     

Virus-specific antibodies to Epstein-Barr virus, varicellazoster virus and rubella virus in renal transplant patients with cytomegalovirus infections

Renal transplant patients with primary and recurrent cytomegalovirus (CMV) infection had higher antibody titres to Epstein-Barr virus viral capsid antigen (EBV-VCA-IgG) before and after transplantation than healthy blood donors. The geometric mean titres (GMT) of EBV-VCA-IgG were higher in renal transplant patients without CMV infection than in renal transplant patients with CMV infection. Four-fold or greater rises in EBV-VCA-IgG antibody were detected in six patients and a similar rise in antibody to EBV early antigen (EBV-EA-IgG) was detected in one other patient. IgM antibody to EBV-VCA (EBV-VCA-IgM) was detected in only three of these patients. EBV-EA-IgG was present in 39% patients and in 30% control subjects. IgG titres to varicella zoster virus (VZV-IgG) and rubella virus (rubella HI) were higher in patients without CMV infection compared to the patients with CMV infection. Raised titres were detected to VZV in five patients and to rubella virus in three patients. Reductions in antibody titre of four-fold or more were also detected in EBV-EA-IgG (one patient) and to rubella virus (one patient). Raised antibody titres to EBV, VZV, and rubella virus in renal transplant patients may indicate reactivation of these viruses without any symptoms.     

No detectable cytomegalovirus and Epstein-Barr virus genomes in the pancreas of recent-onset IDDM patients

Summary Viral infection is assumed to trigger or exacerbate autoimmune responses against pancreatic beta cells leading to the development of insulin-dependent diabetes mellitus (IDDM). We therefore examined by polymerase chain reaction the presence of two candidate viruses, cytomegalovirus and Epstein-Barr virus, in IDDM pancreases. Pancreas tissues were obtained by biopsy under laparoscopy from 16 recent-onset IDDM patients: age 17–53 years; disease duration 0–7 months; six had flu-like symptoms before onset. Frozen sections were made and subjected to DNA amplification. DNA samples were prepared from the frozen sections and polymerase chain reaction was performed using primers specific to cytomegalovirus, Epstein-Barr virus and control gene for HLA-DP. Cytomegalovirus- and Epstein-Barr virus-infected cells were used for positive control. Southern blot analysis could detect cytomegalovirus DNA from as few as 2×10^–1 cytomegalovirus-infected cells and Epstein-Barr virus DNA from two Epstein-Barr virus-infected cells. This highly sensitive analysis, however, could not detect cytomegalovirus or Epstein-Barr virus genomes in pancreases of recent-onset IDDM. A single copy human gene (HLA-DP) was amplified from all IDDM pancreases indicating that DNA amplification was performed without inhibition. We conclude that cytomegalovirus or Epstein-Barr virus genomes are unlikely to exist in pancreas biopsy specimens of recent-onset IDDM patients.Abbreviations CMV Cytomegalovirus - EBV Epstein-Barr virus - IDDM insulin-dependent diabetes mellitus - PCR polymerase chain reaction - ICA islet cell antibodies     

Prevalences of human herpesvirus 6 and human herpesvirus 7 in normal Thai population

Prevalences of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) DNA were investigated in normal Thai population. Peripheral blood mononuclear cells (PBMC) and saliva were collected from 238 healthy adults in five provinces which might be a representative of each part of the country, and 120 normal children in one province. Prevalences of HHV-6 DNA PBMC were 45.5-74.3% in adults and 78.3% in children, and in saliva, very low prevalences were detected; 5.7-8.6% in adults and 15.0% in children, respectively. Additionally, all HHV-6 DNA detected in this study were variant B. Comparingly to those of HHV-7 DNA, the prevalences were significantly higher than those of HHV-6, ie, 82.9-91.4% in PBMC of adults, 85% in PBMC of children, 84.8-89.0% in saliva of adults and 92.5% in saliva of children. HHV-6 and HHV-7 isolation from saliva specimens were also performed. No HHV-6 could be isolated from any samples, whereas, in the present study, HHV-7 could be isolated as 90.0% from children and as 20.0-54.5% from adults.     

Suppression of human immunodeficiency virus type 1 replication by human herpesvirus-6

The pathogenesis of AIDS is complex and poorly understood despite intensive research efforts. One of the most puzzling aspects of the disease is the long interval between primary infection with human immunodeficiency virus (HIV) and the production of antiviral antibodies and onset of overt disease. Probably the most important factor that determines the length of these intervals is the rate at which HIV replicates within the infected host. Molecular studies have suggested that the replication of HIV can be enhanced by concurrent infection with other viruses, especially herpesviruses such as cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. Presumably the presence of those viruses would serve to accelerate the progression of HIV-mediated disease. In contrast, studies reported here indicate that coinfection of cell populations with HIV and human herpesvirus-6 (HHV-6) leads to a near total suppression of HIV replication. The replication of HHV-6 is unaffected or minimally enhanced by the presence of HIV. These findings suggest that HHV-6 might serve to slow the progression of disease in some HIV-infected individuals.     

Coinfection with A- and B-type Epstein-Barr virus in human immunodeficiency virus-positive subjects

A possible cofactor in human immunodeficiency virus (HIV) infection is the Epstein-Barr virus (EBV), which is divided into two primary types that differ significantly in their transformation efficiency. The B-type EBV cell line is much more difficult to establish than the A-type. The extent of systemic B-type EBV infection was assessed in HIV-positive subjects and controls. Lymphoblastoid cell lines were established from 26 HIV-positive subjects and analyzed for the presence of A- or B-type EBV by Southern analysis and immunoblotting. Some 19% of HIV-positive persons were infected with B-type EBV, 69% with A-type, and 12% with both types. Analysis of the individual strains of EBV harbored by the HIV-positive subjects showed that HIV-induced immunosuppression had not led to increased susceptibility to repeated EBV infections. However, the occurrence of B-type infection in HIV-positive subjects was sixfold higher than that in the general community, indicating that HIV-induced immunodeficiency or HIV itself specifically enhanced the expression of the B-type EBV.     

Prevalence of HIV-1 antibody among groups of patients and healthy subjects from a rural and urban population in the Mwanza region, Tanzania

In April 1987, antibody to HIV-1 was determined in sera from 764 subjects from the Mwanza region in the north of Tanzania. Patients with a clinical suspicion of AIDS were HIV-1 antibody-positive in 65.4% (34 out of 52) and patients admitted for pulmonary tuberculosis in 25% (9 out of 36). In patients attending general outpatient departments (OPD), HIV antibody was found in 12.5% of 48 patients with a history of sexually transmitted disease (STD) and in 10.6% of 141 patients without such a history. In healthy subjects, HIV-1 antibody was present in 6% of 332 pregnant women and in 4.5% of 155 blood donors. Of the blood donors, pregnant women and OPD patients without a history of STD (628 subjects in all), 465 belonged to the rural population of the region and the majority were peasants. In this subgroup, the HIV-1 antibody prevalence was 4.8% in blood donors, 4.9% in pregnant women and 10.3% in OPD patients. This indicates a spread of HIV-1 among the population in this part of Tanzania. Further studies are needed to determine what proportion of the population is affected.