Quantitation of Human herpes virus 6 genome in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the main type of leukemia in children. An infectious etiology has been suspected and the role of the Human herpesvirus-6 (HHV-6) has been suggested. Several studies have tried to establish a link between HHV-6 infections and hematological malignancies, with discordant results. The potential role of HHV-6 in the pathogenesis of pediatric acute lymphoblastic leukemia was investigated. HHV-6 genome copy number was measured by quantitative real-time PCR (RQ-PCR) in bone marrow or peripheral blood samples obtained from 36 children (median age = 4 years) with B acute lymphoblastic leukemia (n = 31) and T acute lymphoblastic leukemia (n = 5) at diagnosis and during complete remission. Positive samples were further characterized to define viral variant, A or B. A total of 24.7% of samples were positive for HHV-6 genome: 13.9% were leukemia samples and 34.1% were complete remission samples. Viral load was low with values lower at diagnosis (median viral copy number = 22.9) than at complete remission (median copy number = 60.1). Among the 17 patients with positive samples, 15 were typed as B-variant whereas 2 could not be typed. These results argue against a role of HHV6 infection in the development of pediatric acute lymphoblastic leukemia. They also suggest that HHV-6 may infect latently bone marrow progenitors but seems not able to infect leukemic cells, raising again the question of the mechanism of virus fusion and entry. This observation shows that a reactivation may be observed during complete remission supporting the possibility of virus reactivation in immunocompromised hosts.     

The natural history and laboratory diagnosis of human herpesviruses-6 and -7 infections in the immunocompetent.

BACKGROUND: Human herpesviruses-6 and -7 (HHV-6/7) are widespread in all populations. In some individuals HHV-6 is found integrated into human chromosomes, which results in a high viral load in blood. HHV-6 variant B (HHV-6B) and HHV-7 primary infections, although usually silent, not infrequently cause the childhood exanthem roseola infantum and are sometimes accompanied by neurological illness. HHV-6 variant A (HHV-6A) is not associated with any disease. OBJECTIVES: The present review focuses on the immunocompetent individual and considers the epidemiology of the two viruses and their role as human pathogens. It discusses the importance of satisfactory diagnostic tests to distinguish them, compares those currently available, and recommends how best to differentiate primary from persistent infection in each case. RESULTS: It is explained that at the present time antibody avidity immunofluorescence tests are the most reliable discriminators of the two types of infection. In primary infection these tests can be supplemented by PCR for viral DNA in blood but careful interpretation is required for HHV-6 in view of the high persistent viral DNA load seen with chromosomal integration. Since the contribution of primary HHV-6 and -7 infections to the burden of severe neurological illness in young children is only now emerging as significant, the need to test for these viruses in such cases is stressed. CONCLUSIONS: 1. Primary HHV-6/7 infections must be distinguished from persistent infections. 2. Chromosomal integration of HHV-6 requires urgent study. 3. HHV-6A/B must be distinguished in clinical situations. 4. Where serious neurological disease/encephalitis is temporally related to immunisation it is particularly important to test for HHV-6/7 primary infection since otherwise the condition might wrongly be diagnosed as a vaccine reaction. 5. Because less is currently known about HHV-7 and HHV-6A than HHV-6B, future studies should concentrate on the former two. 6. Improvements in diagnostic tests are required for each virus.     

Unexpected occasional persistence of high levels of HHV-6 DNA in sera: detection of variants A and B

Previously it was thought that in the immunocompetent human herpesvirus-6 [HHV-6] DNA was present transiently in serum during early primary infection but not thereafter. In this study, HHV-6 serum IgG avidity was detected by immunofluorescence and HHV-6 variants A/B [HHV-6A/B] serum DNA by semi-quantitative PCR [titre-log(10) copies/ml] in: (a) young children <3 years old from an encephalitis Survey, and a control Anonymised Serum Bank and (b) children/adults referred for diagnosis. The results showed that 11 out of 15 children [all <2 years] with primary infection proven by seroconversion had transient low levels of serum HHV-6B DNA [mean titre 2.6]. However, 3.3% (6/184) of Survey Children had significantly higher levels [mean titre 5.3; 2 HHV-6A; 4 HHV-6B; P < 0.001]. Similarly high level serum DNA [mean titre 4.0; 4 HHV-6A; 6 HHV-6B] was found in 1.5% (10/653) of the Serum Bank Children. Moreover, seven young children <3 years old [four Survey Children and three referred for diagnosis] had high titre serum HHV-6 DNA [mean 4.8] persisting i.e., in all available samples [median 186 days]. Three older children >3 years old and 4 adults [3 of whom were the mothers of 3 of the young children with persisting HHV-6] also had persisting high titre viral DNA [mean 4.2; median 108 days]. Thus in contrast to acute primary infection, where only HHV-6B DNA is found transiently, both HHV-6A and B DNA persist in serum at high titre in occasional individuals of all ages. The significance of this newly described phenomenon in relation to diagnosis, clinical consequences and congenital infection are discussed.     

The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy

Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are two closely related viruses that can infect cells of the central nervous system (CNS). The similarities between these viruses have made it difficult to separate them on serological level. The broad term HHV-6 remains when referring to studies where the two species were not distinguished, and as such, the seroprevalence is over 90% in the adult population. HHV-6B has been detected in up to 100% of infants with the primary infection roseola infantum, but less is known about the primary infection of HHV-6A. Both viruses are neurotropic and have capacity to establish lifelong latency in cells of the central nervous system, with potential to reactivate and cause complications later in life. HHV-6A infection has been associated with an increased risk of multiple sclerosis (MS), whereas HHV-6B is indicated to be involved in pathogenesis of epilepsy. These two associations show how neurological diseases might be caused by viral infections, but as suggested here, through completely different molecular mechanisms, in an autoimmune disease, such as MS, by triggering an overreaction of the immune system and in epilepsy by hampering internal cellular functions when the immune system fails to eliminate the virus. Understanding the viral mechanisms of primary infection and reactivation and their spectrum of associated symptoms will aid our ability to diagnose, treat and prevent these severe and chronic diseases. This review explores the role of HHV-6A and HHV-6B specifically in MS and epilepsy, the evidence to date and the future directions of this field.     

Primary human herpesvirus 6 infection in young children.

BACKGROUND. Human herpesvirus 6 (HHV-6) is a recently discovered virus that, on the basis of serologic evidence, appears to infect most children by the age of three years. However, the clinical manifestations of primary HHV-6 infection have not been well defined. METHODS. We studied consecutive children two years old or younger who presented to an emergency ward with febrile illnesses. Our evaluation included the isolation of HHV-6 from peripheral-blood mononuclear cells, an immunofluorescent-antibody assay, the detection of HHV-6 by the polymerase chain reaction (PCR), and restriction-endonuclease-fragment profiles of HHV-6 isolates. RESULTS. HHV-6 was isolated from 34 of 243 acutely ill children (14 percent). The children with viremia had irritability, high temperatures (mean, 39.7 degrees C), and inflammation of tympanic membranes (in 21), but few other localizing signs. Two children were hospitalized, but all 34 recovered after an average of four days of fever. The rash characteristic of roseola, which has been associated with HHV-6 infection, was noted in only three children. In 29 children (85 percent), serum samples obtained during convalescence had at least a fourfold increase in IgG antibody titers; 4 infants less than three months old who presumably had maternal antibody did not have this increase. HHV-6 was isolated from blood obtained during convalescence in only one child, but in two thirds of the children the virus could be detected by PCR. The isolates had genomic heterogeneity, indicating the presence of multiple strains. CONCLUSIONS. Primary infection with HHV-6 is a major cause of acute febrile illness in young children. Such infection is associated with varied clinical manifestations, viremia, and the frequent persistence of the viral genome in mononuclear cells.     

Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis

The prevalence and concentration of human herpesvirus 6 (HHV-6) DNA in the cerebrospinal fluid (CSF) of the immunocompetent in primary infection was compared with that in viral chromosomal integration. Samples from 510 individuals with suspected encephalitis, 200 young children and 310 older children and/or adults, and 12 other patients were tested. HHV-6 DNA concentration (log(10) copies/ml) was measured in CSF, serum, and whole blood using PCR. Serum HHV-6 immunoglobulin G antibody was measured by indirect immunofluorescence. Primary infection was defined by antibody seroconversion and/or a low concentration of HHV-6 DNA (<3.0 log(10) copies/ml) in a seronegative serum. Chromosomal integration was defined by a high concentration of viral DNA in serum (>/=3.5 log(10) copies/ml) or whole blood (>/=6.0 log(10) copies/ml). The prevalences of CSF HHV-6 DNA in primary infection and chromosomal integration were 2.5% and 2.0%, respectively, in the young children (<2 years) and 0% and 1.3%, respectively, in the older children and/or adults. The mean concentration of CSF HHV-6 DNA in 9 children with primary infection (2.4 log(10) copies/ml) was significantly lower than that of 21 patients with viral chromosomal integration (4.0 log(10) copies/ml). Only HHV-6B DNA was found in primary infection, whereas in viral integration, 4 patients had HHV-6A and 17 patients HHV-6B. Apart from primary infection, chromosomal integration is the most likely cause of HHV-6 DNA in the CSF of the immunocompetent. Our results show that any diagnosis of HHV-6 encephalitis or other type of active central nervous system infection should not be made without first excluding chromosomal HHV-6 integration by measuring DNA load in CSF, serum, and/or whole blood.     

Detection of human herpesvirus-6 DNA by polymerase chain reaction in serum or plasma.

Human herpesvirus-6 (HHV-6) is a newly identified human pathogen. Currently clinicians rely mainly on blood lymphocyte culture and serological tests to diagnose HHV-6 infection. The polymerase chain reaction (PCR) was carried out on the plasma or sera of patients to determine the value of PCR in the diagnosis of HHV-6 infection. A total of 30 patients entered the study; 10 were experiencing acute HHV-6 infections and 20 were healthy and served as controls. HHV-6 DNA was detected by PCR in the serum or plasma of the 10 cases with acute HHV-6 infections. All 20 controls had no HHV-6 DNA in their sera. The time for serum to become PCR-positive coincided with the appearance of IgG HHV-6 antibody. The relatively late presence of HHV-6 DNA in serum might result from late lysis of infected cells by immune responses. It is concluded that detection of HHV-6 DNA by PCR in the serum is a valuable tool for the diagnosis of acute and/or active viral infection.     

Analysis of human herpesvirus-6 IE1 sequence variation in clinical samples

Herpesvirus immediate early (IE) proteins are known to play key roles in establishing productive infections, regulating reactivation from latency, and creating a cellular environment favourable to viral replication. Human herpesvirus-6 (HHV-6) IE genes have not been studied as intensively as their homologues in the prototype betaherpesvirus human cytomegalovirus (HCMV). Whilst the HCMV IE1 gene is relatively conserved, early studies indicated that HHV-6 IE1 exhibited a high level of sequence variation between HHV-6A and HHV-6B isolates, although the observation was based primarily on virus stocks that had been isolated and propagated in vitro. In this study, we investigated the level of HHV-6 IE1 sequence variation in vivo by direct sequencing of circulating virus in clinical samples without prior in vitro culture. Sequences exactly matching those reported for reference HHV-6 isolates were identified in clinical samples, thus the HHV-6 laboratory strains used in the majority of in vitro studies appear to be representative of virus circulating in vivo with respect to the IE1 gene. The HHV-6 IE1 sequence is also conserved in reference strains that had been passaged extensively in vitro. The high degree of divergence between variant A and B type IE1 sequences was confirmed, but interestingly HHV-6B IE1 sequences were observed to further segregate into two distinct subgroups, with the laboratory strains Z29 and HST representative of these two subgroups. Within each HHV-6B subgroup, a remarkably high level of homology was observed. Thus the HHV-6 IE1 sequence appears highly stable, underlining its potential importance to the viral life cycle.     

Neutralizing antibody responses to human herpesviruses 6 and 7 do not cross-react with each other, and maternal neutralizing antibodies contribute to sequential infection with these viruses in childhood

Seroprevalence of human herpesvirus 6 (HHV-6) and HHV-7 infections is very high throughout the world, and almost all people are exposed first to HHV-6 and second to HHV-7 in their childhood. However, it is not clear whether the neutralizing (NT) antibody response between each virus is cross-reactive or not. To elucidate the NT antibody response between each virus, 55 serum samples from an adult group (subjects 22 to 88 years old) and 60 serum samples from a young group (subjects 2 to 18 years old) were examined by a dot blot method for detecting viral late antigen. Thirty-nine serum samples obtained from cord bloods and a few serum samples obtained from pediatric patients with exanthem subitum were also examined to assess the maternal transferred NT antibodies against each virus. The NT antibody titers against HHV-7 in the adult group remained high throughout all the individuals, and none were negative. Those against HHV-6 were high values in the young group but low values, including negative values (three samples), in the adult group. These results suggested that the NT antibody response to either HHV-6 or HHV-7 in each individual was specific to each virus and did not cross-react with each other. In the adult group, the NT antibody response to HHV-6 decreased, while that to HHV-7 remained high throughout all the individuals. Maternal transferred NT antibody titers against HHV-7 were higher and remained longer after birth than those of HHV-6, and these findings were in accord with the clinical observation that HHV-6 infection usually occurs earlier than HHV-7 infection.     

The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors

A lesser-recognized form of human herpesvirus 6 (HHV-6) persistence is integration of the viral genome in a host chromosome and high viral copy numbers in blood or sera are characteristic of this phenomenon. A cross-sectional study was performed to determine the frequency of high HHV-6 viral loads in whole blood (>6 log(10) copies/ml) in a population of blood donors in London, UK. Blood samples from 500 anonymized blood donors were collected from one donation center, DNA extracted, and quantitative realtime PCR used to measure viral load. Four samples (0.8%) were found to have high viral copy numbers of HHV-6 (median 6.7 log(10) copies/ml; range 6.5- 6.9 log(10) copies/ml). Cellular DNA was also quantitated using qRT-PCR for beta-globin. By comparing these two results, we calculated that there were between two and five copies of HHV-6 present per cell in these four donors. The median viral load detected in plasma from the four individuals was 3.8 log(10) copies/ml (range 3.5-4.0 log(10) copies/ml). All samples were HHV-6 variant B. In addition, a retrospective analysis of all diagnostic blood samples performed for HHV-6 in our center showed a prevalence of 2.9% of high viral loads characteristic of integration. In conclusion, high viral copy numbers of HHV-6, representing a population of viral integration, is detected in 0.8% of UK blood donors. The presence of high HHV-6 viral loads in healthy normal individuals reiterates the need to consider the confounding effect of HHV-6 viral integration in any laboratory diagnosis of HHV-6 infection.     

Human herpesvirus 6 in the pathogenesis of multiple sclerosis

Multiple sclerosis (MS) is one of the most common disabling neurological diseases affecting young adults. It is a chronic disease characterised by inflammation and demyelination. The aetiology of MS is still unknown, but involvement of viruses has been suspected for many years. Recently much interest has focused on human herpesvirus 6 (HHV-6), since the virus has been detected in MS plaques in the brain and patients with MS have been shown to have an aberrant immune response to HHV-6. Results from different studies are, however, conflicting and in the light of the long list of previous claims to have found the viral aetiology of MS it is necessary to interpret the HHV-6 findings with great caution. Possible mechanisms for virally induced demyelination and autoimmunity are discussed in this review, and the evidence for and against a role for HHV-6 in MS is summarised.     

Infections aiguës à herpèsvirus humain 6 (HHV-6) : quand et comment traiter ?

The pathogenicity of human herpesvirus 6 (HHV-6) still raises numerous questions. Acute HHV-6 infections correspond to primary infections, reactivations or exogenous reinfections. The expression of related clinical symptoms is highly variable but may be extremely severe, particularly among immunocompromised patients. The prototypic severe disease associated with these infections is limbic encephalitis occurring in stem cell transplant recipients. The diagnosis of acute HHV-6 infections relies on the quantitation of viral load in whole blood by means of quantitative PCR. The demonstration of HHV-6 causative role in the genesis of clinical symptoms requires additional investigations such as the search for HHV-6 DNA in cerebrospinal fluid in case of encephalitis. The chromosomal integration of HHV-6 DNA is a rare event among HHV-6-infected subjects but may alter the interpretation of virological results. Therapy with ganciclovir, foscarnet or cidofovir has not yet clear indications but, at the current stage of knowledge, only concerns the treatment of highly symptomatic infections. The usefulness of prophylactic or pre-emptive antiviral chemotherapy has not yet been convincingly demonstrated. Treatment efficacy must be checked through a clinical and virological follow up, based in part on quantitative PCR approaches. Controlled studies are urgently needed with the goal of evaluating the cost-effectiveness of HHV-6 follow up and therapy in different clinical situations.     

Fatal adult case of severe lymphocytopenia associated with reactivation of human herpesvirus 6.

It has been suggested that immunosuppression associated with human herpesvirus 6 (HHV-6) infection is a result of functional impairment or direct destruction of immunological cells. The ability of the virus to infect and destroy lymphocytes may cause progressive immunodeficiency in an infant with primary HHV-6 infection. An adult patient is described who had a fatal cytomegalovirus (CMV) infection due to severe and prolonged lymphocyte depletion associated with HHV-6 reactivation. The HHV-6 antibody titers were increased significantly after reactivation, and the virus was isolated from his peripheral blood mononuclear cells. The quantity of both HHV-6 and CMV DNA was determined by using real-time PCR in plasma samples collected serially. HHV-6 DNAemia persisted for 1 month, which started just 1 week after the onset of lymphocytopenia. In contrast to HHV-6, CMV DNAemia was detected in the terminal phase of the illness. Thus, HHV-6 reactivation may have been the cause of the severe lymphocyte depletion and fatal CMV infection.     

Neutralizing Antibody Responses to Human Herpesviruses 6 and 7 Do Not Cross-React with Each Other, and Maternal Neutralizing Antibodies Contribute to Sequential Infection with These Viruses in Childhood

Seroprevalence of human herpesvirus 6 (HHV-6) and HHV-7 infections is very high throughout the world, and almost all people are exposed first to HHV-6 and second to HHV-7 in their childhood. However, it is not clear whether the neutralizing (NT) antibody response between each virus is cross-reactive or not. To elucidate the NT antibody response between each virus, 55 serum samples from an adult group (subjects 22 to 88 years old) and 60 serum samples from a young group (subjects 2 to 18 years old) were examined by a dot blot method for detecting viral late antigen. Thirty-nine serum samples obtained from cord bloods and a few serum samples obtained from pediatric patients with exanthem subitum were also examined to assess the maternal transferred NT antibodies against each virus. The NT antibody titers against HHV-7 in the adult group remained high throughout all the individuals, and none were negative. Those against HHV-6 were high values in the young group but low values, including negative values (three samples), in the adult group. These results suggested that the NT antibody response to either HHV-6 or HHV-7 in each individual was specific to each virus and did not cross-react with each other. In the adult group, the NT antibody response to HHV-6 decreased, while that to HHV-7 remained high throughout all the individuals. Maternal transferred NT antibody titers against HHV-7 were higher and remained longer after birth than those of HHV-6, and these findings were in accord with the clinical observation that HHV-6 infection usually occurs earlier than HHV-7 infection.     

Elucidation of the cross-reactive immunoglobulin M response to human herpesviruses 6 and 7 on the basis of neutralizing antibodies

Human herpesvirus 6 (HHV-6) is closely related to HHV-7 in terms of genome organization and sequence. The cross-reactive responses between HHV-6 and HHV-7 have been reported by using immunofluorescent techniques. Recently we have shown that neutralizing (NT) antibody responses are specific to each virus and do not cross-react. We took advantage of this and used the NT antibody response to estimate the time of seroconversion to each virus and examined the pattern of humoral immune response, especially the immunoglobulin M (IgM) response, against each virus antigen in the natural course of infection with HHV-6 and HHV-7. In children who experienced HHV-6 infection first, followed by HHV-7 infection, the IgM response at the first HHV-6 infection was directed only against HHV-6, while no IgM response was directed against HHV-7 at the second HHV-7 infection. In contrast, in children who experienced HHV-7 infection first, followed by HHV-6 infection, the IgM response at the first HHV-7 infection was directed not only against HHV-7 but also against HHV-6. These data suggest that cross-reactive responses to heterologous viruses should be taken into consideration when making a diagnosis based on IgM antibody.     

A Complex Interaction Between Drug Allergy and Viral Infection

A relationship between viral infections and the simultaneous or subsequent development of drug rashes has been observed in a number of clinical situations. We have recently provided evidence to indicate an intimate relationship between reactivation of human herpesvirus 6 (HHV-6) and the development of a severe systemic hypersensitivity reaction referred to as drug-induced hypersensitivity syndrome (DIHS). This syndrome has several unique features that cannot be explained by a drug etiology; they include its delayed onset, paradoxical worsening of clinical symptoms after discontinuation of the causative drugs, and a step-wise development of several organ system failures long after clinical resolution. Many aspects of this syndrome suggest close similarities between DIHS and graft-versus-host disease (GVHD). Indeed, a wide variety of complications frequently occurring in GVHD, such as autoimmune diseases, is often observed during the course of this syndrome and even long after clinical resolution. Our recent studies have shown that in DIHS sequential reactivations of several herpesviruses (HHV-6, HHV-7, Epstein-Barr virus, and cytomegalovirus) can be detected coincident with various clinical symptoms in the same order as demonstrated in GVHD. Thus, not only the timing but also the order in which these herpesviruses can be reactivated in the host would be crucial determinant of outcomes of the disease. Our results indicate the importance of recognizing DIHS and other drug rashes associated with viral infections at risk of eventually developing autoimmune diseases.     

HHV-6 infection in patients with HIV-1 infection and disease

Human herpesvirus 6 (HHV-6) is among the most widespread of the human herpesviruses. In immunocompetent children, it causes exanthem subitum, febrile episodes without skin rash, and non-Epstein-Barr and non-cytomegalovirus infectious mononucleosis. HHV-6 has also been associated with clinical disease in bone marrow and solid organ transplant recipients. Its potential role in HIV-1-associated clinical syndromes is now being recognized and evaluated. In this review, we describe the virus, the pathogenesis of HHV-6-associated disease, and the diagnostic tests used to differentiate active from latent infection. We then discuss possible clinical manifestations of HHV-6 in HIV-1-infected patients, how to evaluate the need for treatment, and which pharmacologic agents are potentially useful. There is no consensus on these issues in the medical community, and HHV-6 is not now included among indicator infections for the diagnosis of AIDS.     

Controlled study of human herpesvirus 6 detection in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma

Human herpesvirus 6 (HHV-6) is a recently identified lymphotropic herpesvirus, which has been isolated from patients with acquired immunodeficiency syndrome (AIDS) or lymphoproliferative diseases. Two variants A and B of HHV-6 have been described, variant B being more common in children with exanthema subitum. HHV-6 infection was studied in cases of AIDS-associated non-Hodgkin's lymphoma (NHL), and in three control populations in order to evaluate the possible etiologicai role of HHV-6 in this lymphoproliferative disease. Tumor specimens from various organs were obtained from 27 patients with AIDS-associated NHL and 20 human immunodeficiency virus (HlV)-seronegative patients with NHL. Lymph node specimens were obtained from four HIV-seropositive and nine HIV-seronegative patients with lymph node follicular hyperplasia. A specific polymerase chain reaction (PCR) was used to detect HHV-6 DNA. Subsequently HHV-6 variant was identified by using variant-specific PCR. Human cytomegalovirus (CMV) infection was detected in parallel by means of specific PCR. HHV-6 DNA was detected in 12 of 27 tumor tissues (44%), including 8 of 15 lymph node specimens (53%) from patients with AIDS-associated NHL. The corresponding values in HIV-seronegative patients with NHL were 35% (7/20) and 36% (5/14), respectively. Lymph node specimens were positive for HHV-6 in two of four (50%) HIV-seropositive and five of nine (55%) HIV-seronegative patients with follicular hyperplasia. Variant A was detected in two cases of AIDS-associated NHL, variant B in one case, and both variants in six cases. The distribution of HHV-6 variants exhibited a similar pattern in the three control groups. CMV was only detected in 3 of 27 tumor tissues (11%) from patients with AIDS-associated NHL. The prevalence of HHV-6 DNA and the distribution of its variants did not differ significantly among the four populations studied. HHV-6 was more prevalent than CMV, a closely related herpesvirus. Most cases of HHV-6 infection involved both HHV-6 variants A and B. These results do not support strongly that HHV-6 infection is closely associated with the occurrence of NHL in AIDS patients but demonstrate that mixed HHV-6 infections are more common than previously assumed. © 1995 Wiley-Liss, inc.     

Frequent shedding of human herpesvirus 6 in saliva

We have previously reported the isolation of HHV-6 from saliva samples. Because these isolations were made in PHA-stimulated lymphocytes from healthy adults, which may occasionally contain endogenous HHV-6, it was desirable to repeat this work using cord blood lymphocytes. In this study 18 isolations of viruses provisionally characterized as HHV-6 were made from 19 saliva samples by centrifugally enhanced inoculation into PHA-stimulated cord blood lymphocytes. HHV-6 was not found in 10 pernasal aspirates, 50 endocervical swabs, or 30 male urethral swabs. It is concluded that HHV-6 is usually present in the saliva of most adults and that this affords a possible explanation of the high infection rate with this virus in young children.