- Email: [email protected]
26: Chromosomal integration of human herpesvirus 6
S104 Abstracts, 5th Int. Conf. on HHV-6 & 7, 1–3 May 2006, Barcelona, Spain / Journal of Clinical Virology 37 Suppl. 1 (2006) S97–118 26 Chromosomal integration of human herpesvirus 6 D.A. Clark1 *, H.N. Leong2 , E.P. Nacheva3 , E.H.F. Tsao2 , P.D. Griffiths2 , K.N. Ward4 . 1 Department of Virology, Barts and The London NHS Trust, 2 Centre for Virology, 3 Department of Haematology, Hampstead Campus, 4 Centre for Virology, Bloomsbury Campus, Royal Free and University College Medical School, London, UK E-mail address: [email protected] Background: A phenomenon unique to HHV-6 among the human herpesviruses is its integration into host cell chromosomes. Although this has been considered a relatively rare occurrence, viral sequences have previously been identified by fluorescent in situ hybridisation (FISH) on the telomeric ends of chromosomes 1, 17, and 22. An intriguing finding was that these integrated viral sequences can be inherited through the germline. Objectives: To better characterise chromosomally integrated HHV-6 (CIHHV-6). Study Design: An examination of CIHHV-6 prevalence, and to use molecular approaches to characterise biological features of integration and its potential impact in the laboratory diagnosis of HHV-6 infection. Results: To date we have recruited 9 individuals with suspected CIHHV-6. Using FISH analysis on PHA stimulated PBMCs or lymphoblastoid cell lines from 7 of these individuals; we have confirmed chromosomal integration of HHV-6 DNA sequences. In two LCLs tested, PCR analysis of all ORFs in the unique region has shown the entire viral genome to be present. Preliminary analysis of one individual has identified a range of viral transcripts expressed in PBMCs. There are characteristic viral loads associated with CIHHV-6. In whole blood the viral load is >6log10 HHV-6 genomes/ml. In addition, significant viral loads are also present in the CSF of individuals with CIHHV-6. In all these clinical samples there is >1 HHV-6 copy/cell equivalent. Hair follicles have also been HHV-6 DNA PCR positive (>1 HHV-6 genome/cell equivalent) showing inheritance of the integrated sequences. Estimates of the prevalence of CIHHV-6 in the UK population range from 1% to 3% based on our studies in different patient groups and healthy blood donors. Conclusions: These findings highlight the importance of considering CIHHV-6 in the laboratory diagnosis of HHV-6 infection and in studies associating the virus with disease. 27 Detection of HHV-6 in over a thousand samples: new types of infection revealed by the analysis of positive results M. Revest2 , S. Minjolle1 , N. Lafforgue1 , R. Colimon1 *. 1 Laboratoire de Virologie, Centre Hospitalier Universitaire de Rennes, 2 Service de R´eanimation m´edicale, Centre Hospitalier Universitaire de Rennes, France E-mail address: [email protected] Background: HHV-6 has been linked with a variety of human diseases, but the significance of these associations is still discussed. Objectives: To find out the characteristics of HHV-6 infection, we analysed all the samples tested for HHV-6 by PCR at Rennes University Hospital between May 2003 and December 2004. Study Design: Over this period, 1591 PCR were performed, including blood, cerebrospinal fluid, ascitis samples and tissue biopsies. Results: Only 43 of them were positive (3%), corresponding to 25 patients. Three new types of infection were revealed. First, HHV-6 was able to cause severe materno-foetal infections. A young woman presented seroconversion for HHV-6 at 24 weeks pregnancy. The foetus died because of this infection. Postmortem tests demonstrated HHV-6 in all tissues of the foetus, in the umbilical cord blood and in the placenta. HHV-6 was also detected in the mother’s blood by PCR. The second type of infection led to neurological problems, 8 of our patients (36%), including convulsions but also encephalitis and chronic psychiatric troubles in immunocompetent patients. The third type of infection included digestive signs, 10 of our patients (40%). All these
patients were immunocompromised, following liver (4), lung (1) or heart (1) transplantation, corticosteroids treatment (1) or malignant haemopathy (3). The main symptom reported was diarrhea, but two of our patients presented colitis and one of them died due to extensive digestive ulceration, with digestive tract haemorrhage and bacteraemia of gastro-intestinal origin one month after liver transplantation. Conclusions: HHV-6 infection can be sometimes very serious. New types of infection, such as materno-foetal infections, encephalitis in immunocompetent patients and digestive troubles are to be known. 28 Seroprevalences of human herpesviruses 6 and 7 in healthy persons in Slovenia P. Klemenc *, P. Maleˇsiˇc, S. Leviˇcnik-Stezinar, J. Marin. Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljani, Slovenia E-mail address: [email protected] Background: Human herpesvirus (HHV)-6 and HHV-7 are ubiquitous T-lymphotropic viruses that infect most human populations. Infections with either agent occur primarily during childhood. From six months of age, the seropositive rate increases. With age, the serological titer appears to gradually decrease but persists, and the viruses establish lifelong infections. Up to 100% of adult populations are seropositive for HHV-6. A similar pattern exists for HHV-7, although infections appear to occur later during infancy and early childhood, with seropositivity increasing to adulthood. Objectives: To measure IgG anti-HHV-6 and IgG anti-HHV-7 seroprevalence in Slovenia. Study Design: Sera of 100 healthy blood donors from 18 to 65 years of age and sera of 116 healthy children from 9 months to 18 years of age were included. For the detection of IgG anti-HHV-6 EIA was used (Biotrin, Dublin, Ireland) and for IgG anti-HHV-7 IFA (Advanced Biotechnology Incorporated, Columbia, MD, USA). Results: IgG antibodies to HHV-6 were detected in 76% and IgG antibodies to HHV-7 in 68% of sera of healthy blood donors. In 51% both antibodies to HHV-6 and to HHV-7 were detected. Only 7% of blood donors were negative for HHV-6 or HHV-7 antibodies. In healthy children the prevalence rate of IgG anti-HHV-6 was from 70-100% and 30-70% for IgG anti-HHV-7, depending on age. Conclusions: Time is needed to evaluate what the data reveals regarding the pathological potential of the two viruses particularly in immunocompromised individuals. 29 Pediatric HHV-6 infection in Russia N.A. Myukke *, V.K. Tatochenko, T.B. Senzova. Scientific Center of Children’s Health, Moscow, Russia E-mail address: [email protected] Background: The role of Human Herpesvirus 6 as a cause of acute febrile conditions in children has not been adequately studied in Russia. Objective: To study frequency of HHV-6 in children with an acute febrile disease and the prevalence of seropositivity in young children to this virus. Study Design: Nasopharyngeal secretions of 54 children of 6-36 months of age with acute febril illness and fever higher than 390C was studied for HHV-6 by PCR using primers of “DNA-technologies, Russia”. Respiratory viruses were studied by IFA. The prevalence of IgG antibodies was detected in 50 children of the same group by using HHV-6 IgG EIA BIOTRIN; minimal positive titre more than 1.1 UOD. Results: Active HHV-6 infection was detected in 7 children (13%) under 3 years of age. Two children presented exanthema subitum, one child had an exanthema and febrill sezires, two children demonstrated only acute febril illness and one child had symptomatic epilepsy. Other children had respiratory, predominantly adeno- and mixed viral infection. Our serologic study demonstrated that HHV-6 infects
patients were immunocompromised, following liver (4), lung (1) or heart (1) transplantation, corticosteroids treatment (1) or malignant haemopathy (3). The main symptom reported was diarrhea, but two of our patients presented colitis and one of them died due to extensive digestive ulceration, with digestive tract haemorrhage and bacteraemia of gastro-intestinal origin one month after liver transplantation. Conclusions: HHV-6 infection can be sometimes very serious. New types of infection, such as materno-foetal infections, encephalitis in immunocompetent patients and digestive troubles are to be known. 28 Seroprevalences of human herpesviruses 6 and 7 in healthy persons in Slovenia P. Klemenc *, P. Maleˇsiˇc, S. Leviˇcnik-Stezinar, J. Marin. Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljani, Slovenia E-mail address: [email protected] Background: Human herpesvirus (HHV)-6 and HHV-7 are ubiquitous T-lymphotropic viruses that infect most human populations. Infections with either agent occur primarily during childhood. From six months of age, the seropositive rate increases. With age, the serological titer appears to gradually decrease but persists, and the viruses establish lifelong infections. Up to 100% of adult populations are seropositive for HHV-6. A similar pattern exists for HHV-7, although infections appear to occur later during infancy and early childhood, with seropositivity increasing to adulthood. Objectives: To measure IgG anti-HHV-6 and IgG anti-HHV-7 seroprevalence in Slovenia. Study Design: Sera of 100 healthy blood donors from 18 to 65 years of age and sera of 116 healthy children from 9 months to 18 years of age were included. For the detection of IgG anti-HHV-6 EIA was used (Biotrin, Dublin, Ireland) and for IgG anti-HHV-7 IFA (Advanced Biotechnology Incorporated, Columbia, MD, USA). Results: IgG antibodies to HHV-6 were detected in 76% and IgG antibodies to HHV-7 in 68% of sera of healthy blood donors. In 51% both antibodies to HHV-6 and to HHV-7 were detected. Only 7% of blood donors were negative for HHV-6 or HHV-7 antibodies. In healthy children the prevalence rate of IgG anti-HHV-6 was from 70-100% and 30-70% for IgG anti-HHV-7, depending on age. Conclusions: Time is needed to evaluate what the data reveals regarding the pathological potential of the two viruses particularly in immunocompromised individuals. 29 Pediatric HHV-6 infection in Russia N.A. Myukke *, V.K. Tatochenko, T.B. Senzova. Scientific Center of Children’s Health, Moscow, Russia E-mail address: [email protected] Background: The role of Human Herpesvirus 6 as a cause of acute febrile conditions in children has not been adequately studied in Russia. Objective: To study frequency of HHV-6 in children with an acute febrile disease and the prevalence of seropositivity in young children to this virus. Study Design: Nasopharyngeal secretions of 54 children of 6-36 months of age with acute febril illness and fever higher than 390C was studied for HHV-6 by PCR using primers of “DNA-technologies, Russia”. Respiratory viruses were studied by IFA. The prevalence of IgG antibodies was detected in 50 children of the same group by using HHV-6 IgG EIA BIOTRIN; minimal positive titre more than 1.1 UOD. Results: Active HHV-6 infection was detected in 7 children (13%) under 3 years of age. Two children presented exanthema subitum, one child had an exanthema and febrill sezires, two children demonstrated only acute febril illness and one child had symptomatic epilepsy. Other children had respiratory, predominantly adeno- and mixed viral infection. Our serologic study demonstrated that HHV-6 infects