Presence Of Human Herpesvirus Research Articles

Presence of humanherpes virus 8 in the plaques of multiple sclerosis patients

Presence of humanherpes virus 8 in the plaques of multiple sclerosis patients

Human herpesvirus 8 detection in nasal secretions and saliva.

The presence of human herpesvirus 8 (HHV-8) was determined by polymerase chain reaction (PCR) in nasal secretions and saliva from 14 HHV-8-seropositive persons, including 8 Kaposi's sarcoma patients: 7 were human immunodeficiency virus type 1-infected, 6 of whom were asymptomatic. HHV-8 was detected in one or both body fluids in 8 (57%) of 14 subjects. Parallel PCR testing revealed the concomitant presence of cytomegalovirus, Epstein-Barr virus, and HHV-6 in various combinations in these body fluids. These data indicate frequent shedding of multiple herpesviruses in nasal secretions and saliva, particularly in Kaposi's sarcoma patients. Both body fluids are therefore potential sources HHV-8 by nonsexual transmission.

Presence of human herpesvirus 8 is specific to Kaposi's sarcoma lesion

Presence of human herpesvirus 8 is specific to Kaposi's sarcoma lesion

Presence of human herpesvirus 8 variants in the oral tissues of human immunodeficiency virus-infected persons.

A 210-bp DNA segment specific to the human herpesvirus 8 (HHV-8) genome was amplified by nested polymerase chain reaction from 10 of 14 archived oral biopsy samples of HIV-positive patients in London who had no evidence of oral Kaposi's sarcoma (KS). Various oral sites were represented. Oral tissues from 20 general dental patients not known to be HIV-infected were negative. When DNA sequences of these products were compared with sequences derived from 5 oral KS tissues of AIDS patients in London and 10 skin biopsies of Italian patients with Mediterranean KS (total number of positive tissues = 25), 11 were found to be unique. DNA and predicted peptide motifs of these sequences were also different from those in 28 of 36 HHV-8-positive lesions previously reported from American and African patients. HHV-8 is tropic for the oral mucosa of HIV-infected persons, and HHV-8 variants, though diverse, may be geographically restricted.

Presence of human herpesvirus 6 variants A and B in saliva and peripheral blood mononuclear cells of healthy adults.

Saliva and peripheral blood mononuclear cells (PBMCs) from 44 healthy young adults were tested for human herpesvirus 6 variants A and B (HHV-6A and -6B) DNA by a sensitive nested PCR. HHV-6B infection was ascertained in 98% of the subjects, and 95% were found to excrete variant B in their saliva. HHV-6A was found in the PBMCs of 16%, but was not detected in saliva samples.

Detection of human herpesvirus 6 sequences in lymphoma tissues by immunohistochemistry and polymerase chain reactions.

We have analyzed one Hodgkin's and six non-Hodgkin's lymphomas for the presence of human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR) and antigens by immunohistochemistry. A large cell B-cell lymphoma and a T-cell lymphoma were positive for HHV-6 antigens by immunohistochemistry. Using PCR primers from the HHV-6 ZVH14 transforming DNA segment, all seven tumors were positive. EBV DNA was not detected by PCR using sequences from EBV internal repeat-3 region as primers. The data suggest an etiologic involvement of HHV-6 in some human lymphomas. Although all seven of the lymphoma tissues examined contained HHV-6 DNA, expression of HHV-6 antigens was observed in only two cases, suggesting that expression of proteins was not required for transformation.

Detection of human herpesvirus 8 DNA sequences before the appearance of Kaposi's sarcoma in human immunodeficiency virus (HIV)-positive subjects with a known date of HIV seroconversion.

The presence of human herpesvirus 8 (HHV-8) DNA sequences was sought by polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 4 groups: 6 human immunodeficiency virus (HIV)-infected persons with well-defined dates of seroconversion, during the period between the diagnosis of HIV infection and the appearance of Kaposi's sarcoma (KS); 45 HIV-positive persons with no symptoms of HIV infection; 11 AIDS patients with KS; and 14 AIDS patients without KS. HHV-8 DNA PCR was positive in 3 of the 6 patients during HIV infection preceding the appearance of KS and in all but 1 of 11 AIDS patients with KS. HHV-8 DNA PCR was negative in all but 1 of the 45 HIV-positive persons with no symptoms of infection and in all but 1 AIDS patient without KS. These results indicate that HHV-8 DNA may be detected several years before the occurrence of KS in HIV-infected subjects.

Search for human herpesvirus 6 and human cytomegalovirus in bronchoalveolar lavage from patients with human immunodeficiency virus-1 and respiratory disorders.

Virus isolation and viral DNA detection by the polymerase chain reaction were used to investigate the presence of human herpesvirus 6 (HHV-6) and human cytomegalovirus (HCMV) in bronchoalveolar lavage from 34 human immunodeficiency virus-1 (HIV-1)-infected patients with respiratory disorders. The aim was to assess the presence of reactivated HHV-6 in lung tissues for a subsequent evaluation of the frequency of virus involvement in respiratory clinical manifestations in the course of HIV-1 infection. Bronchoalveolar lavage samples were tested for the presence of HCMV, as a routine investigation within a protocol monitoring opportunistic infections in symptomatic HIV-1 patients. Whereas HCMV DNA was detected by the polymerase chain reaction in 12 bronchoalveolar lavage specimens, 10 of which were also positive for virus isolation, all samples were negative for HHV-6 by both virological procedures. The HHV-6 DNA finding in bronchoalveolar lavage from an HIV-1-seronegative patient with renal carcinoma, investigated accidentally together with the bronchoalveolar lavage specimens from HIV-1 seropositive patients, stressed the HHV-6 polymerase chain reaction-negative results in the bronchoalveolar lavage samples under study. It is concluded that the lung may be a target organ for HCMV infection in HIV-1-seropositive patients affected by respiratory symptoms but that this does not seem to be the case for HHV-6.

Seroepidemiological study of human herpesvirus-6 and -7 in children of different ages and detection of these two viruses in throat swabs by polymerase chain reaction.

The presence of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) in throat swabs of 62 children of different age groups (group I, ages 0-5 month; group II, ages 6-11 months, group III, ages 12-23 months, group IV, age 2-8 years) and 28 adults was detected by polymerase chain reaction. The detection rate of HHV-6 DNA was the highest (87%) in children aged 1-year-old and decreased with age, whereas the detection rate of HHV-7 increased with age and reached a maximum in adults. HHV-6B was detected in almost all samples except for two children who secreted only HHV-6A. When the antibody prevalence was determined in the four groups of children, HHV-6 antibody was detected in 8/12 (66.7%), 10/12 (83.3%), 15/16 (93.8%), and 13/14 (92.9%), respectively. Antibody to HHV-7 in these groups was detected in 6/12 (50.0%), 4/12 (33.3%), 12/16 (75.0%), and 13/14 (92.9%), respectively. Detection of HHV-6 DNA in throat swabs of triplets who had the sequential onset of exanthem subitum was attempted by using samples sequentially collected from these children after the onset of the disease in the first patient. HHV-6 DNA with high copy numbers was detectable during the acute and convalescent phases of the disease in all patients, but no DNA was detected in samples collected before the onset of disease.

Rate of detection of human herpesvirus-6 at different stages of HIV infection.

In a cross-sectional study, human herpesvirus-6 (HHV-6) infection was analysed by means of polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) and saliva from 125 HIV-seropositive subjects and 29 HIV-seronegative controls. HHV-6 was detected in saliva significantly more frequently in HIV-seronegative subjects than in HIV-seropositive subjects (p = 0.023), with no significant difference between HIV-seropositive subgroups. The HIV proviral copy number in PBMCs differed significantly according to HIV subgroup, as expected, but did not differ according to either the presence of HHV-6 or the number of HHV-6 copies in PBMCs. All the HHV-6 identified were variant B except for one variant A strain detected in saliva from a healthy subject. These results do not support the hypothesis that there is synergistic activation of HHV-6 infection in the course of HIV infection.

Diagnosis of human herpesvirus-6 infection in two patients with central nervous system complications

Background: Although exanthem subitum (ES) is generally a mild, self-limiting disease of early childhood, some cases of ES are complicated by seizures and encephalopathy. The presence of human herpesvirus-6 (HHV-6) DNA in cerebrospinal fluid (CSF) of these patients suggests that HHV-6 can infect the central nervous system (CNS) causing encephalitis. Objectives: To demonstrate HHV-6 infection in two patients with serious CNS complications. The patients, a child and an adult, failed to develop the characteristic rash normally associated with ES. Study design: Peripheral blood mononuclear cells (PBMCs) and CSF were examined for the presence of HHV-6 or viral DNA, using virus isolation techniques and the polymerase chain reaction (PCR). Serum samples were tested by immunofluorescence (IF) and enzyme linked immuno-sorbent assay (ELISA) for the presence of anti-HHV-6 IgM and anti-HHV-6 IgG respectively. Results: HHV-6 was isolated from the PBMCs of the adult patient and the presence of virus in these cells was confirmed using electron microscopy. HHV-6 DNA was detected in CSF taken early during the infection in both patients, together with anti-HHV-6 IgM antibodies and increasing levels of anti-HHV-6 IgG. Conclusions: The diagnosis of HHV-6 infection in these patients was confirmed either by virus isolation or by the detection of HHV-6 DNA in the CSF, and the results of serology. These cases show that HHV-6 infection may result in serious CNS complications, in children and adults.

Human herpesviruses 6 and 7 in salivary glands and shedding in saliva of healthy and human immunodeficiency virus positive individuals

The presence of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) was investigated by the polymerase chain reaction in saliva specimens from healthy persons, donors affected by common cold or recurrent aphthous ulceration (RAU), and human immunodeficiency virus (HIV) positive patients, and in salivary gland biopsies. The sensitivity of the technique made it possible to detect as few as 5-10 target molecules in 15 microliters of saliva. HHV-6 was present in 63% of salivary gland biopsies and in 3% of salivas from healthy persons. No significant difference in the presence of HHV-6 was detected in specimens from donors with common cold, RAU, or HIV-infected patients. HHV-7 was present in 75% of salivary glands and in 55% of salivas from healthy persons. HHV-7 was detected with similar frequency in salivas from donors with common cold or RAU. Salivas from HIV-infected patients harbored HHV-7 with higher frequency (81%) and increased viral load. These results show that salivary glands are a site of persistent infection for both HHV-6 and HHV-7. However, the two viruses seem to differ in their biological properties: 1) HHV-6 is rarely present in saliva in detectable amounts, while HHV-7 is frequently detected; and 2) immunosuppression by acquired immunodeficiency syndrome (AIDS) increases the frequency of detection and the viral load of HHV-7, but does not have a significant effect on HHV-6 shedding in saliva.

A Model to Study Viral and Cytokine Involvement in Sjogren's Syndrome

To investigate mechanisms that may be important in the pathogenesis of Sjögren's syndrome (SS) we developed a protocol for the growth of salivary gland epithelial cells in culture. We examined the effect that viral infection has on the cellular location of the autoantigen La. Autoantibodies to La are common in SS and it has been proposed that viral infection may result in cell membrane expression of La. Co-expression of MHC class II molecules in infected cells could lead to the presentation of La peptides to the immune system. Advenovirus infection of salivary gland epithelial cells resulted in an altered nuclear staining of La. Treatment with interferon-gamma resulted in the expression of La in the cell cytoplasm and HLA-DR molecules at the cell surface. These findings suggest that a cytokine-driven mechanism may generate an autoimmune response to La in SS. Using the polymerase chain reaction (PCR) we tested salivary gland epithelial cell cultures for the presence of human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). Only HHV-6 was detected in 2 of 10 salivary gland epithelial cell cultures although the presence of HHV-6 was not associated with SS. Primary salivary gland cultures may prove useful as an in vitro model to study mechanisms of autoimmunity in SS.

Lymphadenitis and lymphoproliferative lesions associated with the human herpes virus-6 (HHV-6)

A newly described herpes virus, human herpes virus 6, (HHV-6), has been linked to exanthema subitum but beyond this its pathogenetic impact remains to be determined. A large body of evidence links it to various lymphoproliferative disorders and this study was conducted to identify forms of lymphoproliferation linked to HHV-6. We studied biopsy samples from 32 patients with disorders of the lymphatic system for the presence of HHV-6, both by polymerase chain reaction (PCR) and in-situ hybridization (ISH) methods, as well as Epstein-Barr virus (EBV) viral DNA, clonal rearrangements of the antigen receptor genes and bcl-2 genes. All the specimens were studied morphologically and a clinical follow-up of up to 4 years was obtained. Seven of the 32 patients were positive for HHV-6 DNA and the remainder were negative. Two of these HHV-6 positive specimens, both from elderly persons, showed a similar distinct histological pattern diagnosed as malignant B-cell lymphoma of high grade malignancy. Two other HHV-6-positive specimens were reactive lymphadenopathies occurring in younger adults. In addition, one further specimen with evidence of EBV-involvement was from a patient who died 3 months after biopsy with fatal infectious mononucleosis (IM). These five samples had HHV-6 DNA by PCR and ISH. Two specimens without specific histologic abnormalities showed evidence of HHV-6 only by PCR but not by ISH. Both high grade malignant lymphomas showed clonal proliferations, one of monoclonal B-cells and the other of clonal T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulatory effects of Epstein-Barr, herpes simplex, and human herpes-6 viral infections and coinfections on cytokine synthesis. A comparative study.

Herpesviruses such as EBV, HSV, and human herpes virus-6 (HHV-6) have a marked tropism for cells of the immune system and therefore infection by these viruses may result in alterations of immune functions, leading at times to a state of immunosuppression. We report the results of a comparative study in which we found that EBV, HSV-1, and HHV-6 act differentially on the immune system with regard to their effect on the synthesis of IL-1 beta, IL-6, and TNF-alpha, i.e., three immunoregulatory cytokines mainly secreted by activated monocytes/macrophages. Using the polymerase chain reaction technique, analyses of the mRNA levels for each of the three monokines after viral infection indicated that the effect exerted by each of these herpesviruses on cytokine synthesis by human PBMC was detectable at the transcriptional level. Different amounts of IL-1 beta protein were detected in infected PBMC cultures, HHV-6 being the strongest IL-1 beta up-regulatory among these three herpesviruses. Spontaneous releases of IL-6 and TNF-alpha were found reduced after infection by HHV-6 and EBV, respectively. In comparison to EBV and HHV-6, HSV-1 proved to be a weak monokine enhancer. Results of coinfection studies indicated that virus-induced suppressive effects on cytokine synthesis are dominant. In fact, EBV inhibited TNF-alpha synthesis even in the presence of HHV-6, a strong up-regulator of TNF-alpha synthesis. Similarly, EBV was unable to stimulate IL-6 production in the presence of HHV-6. Viral structural component(s) appeared to be responsible for the up-regulation of IL-6 by both EBV and HSV-1, and of TNF-alpha by HSV-1. Taken together, our observations illustrate that herpesviruses can selectively regulate cytokine synthesis thereby disturbing immune homeostasis; this effect may favor pathogenic events, including the reactivation and/or spread of other infectious agents within the host.