Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-f554764f5-68cz6 Total loading time: 0 Render date: 2025-04-19T09:49:26.865Z Has data issue: false hasContentIssue false

49 - HHV-6A, 6B, and 7: persistence in the population: epidemiology and transmission

from Part III - Pathogenesis, clinical disease, host response, and epidemiology: HHV- 6A, 6B, and 7

Published online by Cambridge University Press:  24 December 2009

By
Vincent C. Emery  and
Duncan A. Clark
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
Vincent C. Emery
Affiliation:
Department of Virology, Royal Free and University College Medical School of UCL, London, UK
Duncan A. Clark
Affiliation:
Department of Virology, Royal Free and University College Medical School of UCL, London, UK
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
Get access

Summary

Introduction

In common with all human herpesviruses, HHV-6 and HHV-7 establish lifelong infection following initial exposure and seroconversion. True latency as exemplified by HSV-1 and VZV, in which the genome is maintained in a transcriptionally restricted state, has not been conclusively shown for HHV-6 or HHV-7. However, the betaherpesviruses may persist in individuals via low grade replication which is continuously suppressed by a functional immune response. In this chapter we will summarize the current understanding of the epidemiology and persistence of HHV-6 and HHV-7 in the human host and its relevance to transmission. In addition, we will highlight a novel form of persistence for HHV-6 which involves integration into host chromosomal DNA.

Persistence of HHV-6 and HHV-7 in individuals

In the case of both HHV-6 and HHV-7, PCR analysis of peripheral blood mononuclear cells (PBMC) shows that a sensitive nested assay and an adequate quantity of input DNA (at least equivalent to approximately 150000 mononuclear cells or 1μg DNA) can detect viral DNA in healthy immunocompetent individuals suggestive of low levels of latent/persisting virus in peripheral blood (Jarrett et al., 1990; Clark et al., 1996; Kidd et al., 1996). In contrast, viral loads are maintained at high levels in saliva of seropositive individuals, particularly in the case of HHV-7 (Kidd et al., 1996; Fujiwara et al., 2000; see Fig. 49.1).

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 875 - 882
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Aberle, S. W., Mandl, C. W., Kunz, C., and Popow-Kraupp, T. (1996). Presence of human herpesvirus 6 variants A and B in saliva and peripheral blood mononuclear cells of healthy adults. J. Clin. Microbiol., 34, 3223–3225.Google Scholar
Adams, O., Krempe, C., Kogler, G., Wernet, P., and Scheid, A. (1998). Congenital infections with human herpesvirus 6. J. Infect. Dis., 178, 544–546.CrossRefGoogle ScholarPubMed
Aubin, J. T., Poirel, L., Agut, H.et al. (1992). Intrauterine transmission of human herpesvirus 6 [letter]. Lancet, 340, 482–483.CrossRefGoogle Scholar
Black, J. B., Schwarz, T. F., Patton, J. L.et al. (1996). Evaluation of immunoassays for detection of antibodies to human herpesvirus 7. Clin. Diag. Lab. Immunol., 3, 79–83.Google ScholarPubMed
Caserta, M. T., Hall, C. B., Schnabel, K.et al. (1994). Neuroinvasion and persistence of human herpesvirus 6 in children. Journal of Infectious Diseases, 170, 1586–1589.CrossRefGoogle ScholarPubMed
Chan, P. K., Ng, H. K., Hui, M., and Cheng, A. F. (2001). Prevalence and distribution of human herpesvirus 6 variants A and B in adult human brain. J. Med. Virol., 64, 42–46.CrossRefGoogle Scholar
Chiu, S. S., Cheung, C. Y., Tse, C. Y., and Peiris, M. (1998). Early diagnosis of primary human herpesvirus 6 infection in childhood: serology, polymerase chain reaction, and virus load. J. Infect. Dis., 178, 1250–1256.CrossRefGoogle ScholarPubMed
Chou, S. and Marousek, G. I. (1994). Analysis of interstrain variation in a putative immediate-early region of human herpesvirus 6 DNA and definition of variant-specific sequences. Virology, 198, 370–376.CrossRefGoogle Scholar
Clark, D. A., Ait-Khaled, M., Wheeler, A. C.et al. (1996). Quantification of human herpesvirus 6 in immunocompetent persons and post-mortem tissues from AIDS patients by PCR. J. Gen. Virol., 77, 2271–2275.CrossRefGoogle ScholarPubMed
Clark, D. A., Kidd, I. M., and Collingham, K. E. (1997). Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction. Arch. Dis. Child., 77, 42–45.CrossRefGoogle ScholarPubMed
Clark, D. A., Nacheva, E. P., Leong, H. N.et al. (2006).Transmission of integrated human herpesvirus 6 through stem cell transplantation: implications for laboratory diagnosis. J. Infect. Dis., 193, 912–916.CrossRefGoogle ScholarPubMed
Cone, R. W., Huang, M. L., Hackman, R. C., and Corey, L. (1996). Coinfection with human herpesvirus 6 variants A and B in lung tissue. J. Clin. Microbiol., 34, 877–881.Google Scholar
Dahl, H., Fjaertoft, G., Norsted, T., Wang, F. Z., Mousavi-Jazi, M., and Linde, A. (1999). Reactivation of human herpesvirus 6 during pregnancy. J. Infect. Dis., 180, 2035–2038.CrossRefGoogle ScholarPubMed
Daibata, M., Taguchi, T., Taguchi, H., and Miyoshi, I. (1998). Integration of human herpesvirus 6 in a Burkitt's lymphoma cell line. Br. J. Haematol., 102, 1307–1313.CrossRefGoogle Scholar
Daibata, M., Taguchi, T., Nemoto, Y., Taguchi, H., and Miyoshi, I. (1999). Inheritance of chromosomally integrated human herpesvirus 6 DNA. Blood, 94, 1545–1549.Google ScholarPubMed
Dewhurst, S., Chandran, B., McIntyre, K., Schnabel, K., and Hall, C. B. (1992). Phenotypic and genetic polymorphisms among human herpesvirus-6 isolates from North American infants. Virology, 190, 490–493.CrossRefGoogle ScholarPubMed
Dewhurst, S., McIntyre, K., Schnabel, K., and Hall, C. B. (1993). Human herpesvirus 6 (HHV-6) variant B accounts for the majority of symptomatic primary HHV-6 infections in a population of U.S. infants. J. Clin. Microbiol., 31, 416–418.Google Scholar
Luca, D., Dolcetti, R., and Mirandola, P. (1994). Human herpesvirus 6: a survey of presence and variant distribution in normal peripheral lymphocytes and lymphoproliferative disorders. J. Infect. Dis., 170, 211–215.CrossRefGoogle ScholarPubMed
Luca, D., Mirandola, P., Ravaioli, T., Bigoni, B., and Cassai, E. (1996). Distribution of HHV-6 variants in human tissues. [Review] [103 refs]. Infect. Agents and Dis., 5, 203–214.Google Scholar
Dominguez, G., Dambaugh, T. R., Stamey, F. R., Dewhurst, S., Inoue, N., and Pellett, P. E. (1999). Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. Journal of Virology, 73, 8040–8052.Google ScholarPubMed
Emery, V. C., Atkins, M. C., Bowen, E. F.et al. (1999). Interactions between beta-herpesviruses and human immunodeficiency virus in vivo: evidence for increased human immunodeficiency viral load in the presence of human herpesvirus 6. J. Med. Virol., 57, 278–282.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Franti, M., Gessain, A., Darlu, P.et al. (2001). Genetic polymorphism of human herpesvirus-7 among human populations. J. Gen. Virol., 82, 3045–3050.CrossRefGoogle ScholarPubMed
Fujisaki, H., Tanaka-Taya, K., Tanabe, H.et al. (1998). Detection of human herpesvirus 7 (HHV-7) DNA in breast milk by polymerase chain reaction and prevalence of HHV-7 antibody in breast-fed and bottle-fed children. J. Med. Virol., 56, 275–279.3.0.CO;2-D>CrossRefGoogle ScholarPubMed
Fujiwara, N., Namba, H., Ohuchi, R.et al. (2000). Monitoring of human herpesvirus-6 and -7 genomes in saliva samples of healthy adults by competitive quantitative PCR. J. Med. Virol., 61, 208–213.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Gautheret-Dejean, A., Dejean, O., Vastel, L.et al. (2000). Human herpesvirus-6 and human herpesvirus-7 in the bone marrow from healthy subjects. Transplantation, 69, 1722–1723.CrossRefGoogle ScholarPubMed
Gompels, U. A., Carrigan, D. R., Carss, A. L., and Arno, J. (1993). Two groups of human herpesvirus 6 identified by sequence analyses of laboratory strains and variants from Hodgkin's lymphoma and bone marrow transplant patients. J. Gen. Virol., 74, 613–622.CrossRefGoogle ScholarPubMed
Gompels, U. A., Nicholas, J., Lawrence, G.et al. (1995). The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. [Review] [196 refs]. Virology, 209, 29–51.CrossRefGoogle Scholar
Hall, C. B., Long, C. E., Schnabel, K. C.et al. (1994). Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N. Engl. J. Med., 331, 432–438.CrossRefGoogle ScholarPubMed
Hall, C. B., Caserta, M. T., Schnabel, K. C.et al. (1998). Persistence of human herpesvirus 6 according to site and variant: possible greater neurotropism of variant A. Clin. Infect. Dis., 26, 132–137.CrossRefGoogle ScholarPubMed
Isegawa, Y., Mukai, T., and Nakano, K. (1999). Comparison of the complete DNA sequences of human herpesvirus 6 variants A and B. J. Virol., 73, 8053–8063.Google ScholarPubMed
Jarrett, R. F., Clark, D. A., Josephs, S. F., and Onions, D. E. (1990). Detection of human herpesvirus-6 DNA in peripheral blood and saliva. J. Med. Virol., 32, 73–76.CrossRefGoogle ScholarPubMed
Kasolo, F. C., Mpabalwani, E., and Gompels, U. A. (1997). Infection with AIDS-related herpesviruses in human immunodeficiency virus-negative infants and endemic childhood Kaposi's sarcoma in Africa. J. Gen. Virol., 78, 847–855.CrossRefGoogle ScholarPubMed
Kidd, I. M., Clark, D. A., Ait-Khaled, M., Griffiths, P. D., and Emery, V. C. (1996). Measurement of human herpesvirus 7 load in peripheral blood and saliva of healthy subjects by quantitative polymerase chain reaction. J. Infect. Dis., 174, 396–401.CrossRefGoogle ScholarPubMed
Kidd, I. M., Clark, D. A., Bremner, J. A., Pillay, D., Griffiths, P. D., and Emery, V. C. (1998). A multiplex PCR assay for the simultaneous detection of human herpesvirus 6 and human herpesvirus 7, with typing of HHV-6 by enzyme cleavage of PCR products. J. Virol. Methods, 70, 29–36.CrossRefGoogle ScholarPubMed
Kondo, K., Shimada, K., Sashihara, J., Tanaka-Taya, K., and Yamanishi, K. (2002) Identification of human herpesvirus 6 latency-associated transcripts. J. Virol., 76, 4145–4151.CrossRefGoogle ScholarPubMed
Lanari, M., Papa, I., Venturi, V.et al. (2003). Congenital infection with human herpesvirus 6 variant B associated with neonatal seizures and poor neurological outcome. J. Med. Virol., 70, 628–632.CrossRefGoogle ScholarPubMed
Lau, Y. L., Peiris, M., Chan, G. C., Chan, A. C., Chiu, D., and Ha, S. Y. (1998). Primary human herpes virus 6 infection transmitted from donor to recipient through bone marrow infusion. Bone Marrow Transplantation, 21, 1063–1066.CrossRefGoogle ScholarPubMed
Lunel, F., Agut, H., Robert, C.et al. (1991). Is human herpes virus 6 (HHV-6) infection associated with posttransfusion hepatitis?Transfusion, 31, 872.CrossRefGoogle Scholar
Luppi, M., Marasca, R., Barozzi, P.et al. (1993). Three cases of human herpesvirus-6 latent infection: integration of viral genome in peripheral blood mononuclear cell DNA. J. Med. Virol., 40, 44–52.CrossRefGoogle ScholarPubMed
Megaw, A. G., Rapaport, D., Avidor, B., Frenkel, N., and Davison, A. J. (1998). The DNA sequence of the RK strain of human herpesvirus 7. Virology, 244, 119–132.CrossRefGoogle ScholarPubMed
Mori, Y., Seya, T., Huang, H. L., Akkapaiboon, P., Dhepakson, P., and Yamanishi, K. (2002). Human herpesvirus 6 variant A but not variant B induces fusion from without in a variety of human cells through a human herpesvirus 6 entry receptor, CD46. J. Virol., 76, 6750–6761.CrossRefGoogle ScholarPubMed
Mori, Y., Yang, X., Akkapaiboon, P., Okuno, T., and Yamanishi, K. (2003). Human herpesvirus 6 variant A glycoprotein H-glycoprotein L-glycoprotein Q complex associates with human CD46. J. Virol., 77, 4992–4999.CrossRefGoogle ScholarPubMed
Morris, C., Luppi, M., McDonald, M., Barozzi, P., and Torelli, G. (1999). Fine mapping of an apparently targeted latent human herpesvirus type 6 integration site in chromosome band 17p13.3. J. Med. Virol., 58, 69–75.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Okuno, T., Takahashi, K., Balachandra, K.et al. (1989). Seroepidemiology of human herpesvirus 6 infection in normal children and adults. J. Clin. Microbiol., 27, 651–653.Google ScholarPubMed
Okuno, T., Oishi, H., Hayashi, K., Nonogaki, M., Tanaka, K., and Yamanishi, K. (1995). Human herpesviruses 6 and 7 in cervixes of pregnant women. J. Clin. Microbiol., 33, 1968–1970.Google ScholarPubMed
Rapp, J. C., Krug, L. T., Inoue, N., Dambaugh, T. R., and Pellett, P. E. (2000). U94, the human herpesvirus 6 homolog of the parvovirus nonstructural gene, is highly conserved among isolates and is expressed at low mRNA levels as a spliced transcript. Virology, 268, 504–516.CrossRefGoogle ScholarPubMed
Sada, E., Yasukawa, M., Ito, C.et al. (1996). Detection of human herpesvirus 6 and human herpesvirus 7 in the submandibular gland, parotid gland, and lip salivary gland by PCR. J. of Clini. Microbiol., 34, 2320–2321.Google ScholarPubMed
Santoro, F., Kennedy, P. E., Locatelli, G., Malnati, M. S., Berger, E. A., and Lusso, P. (1999). CD46 is a cellular receptor for human herpesvirus 6. Cell, 99, 817–827.CrossRefGoogle ScholarPubMed
Santoro, F., Greenstone, H. L., Insinga, A.et al. (2003). Interaction of glycoprotein H of human herpesvirus 6 with the cellular receptor CD46. J. Biol. Chem., 278, 25964–25969.CrossRefGoogle ScholarPubMed
Suga, S., Yazaki, T., Kajita, Y., Ozaki, T., and Asano, Y. (1995). Detection of human herpesvirus 6 DNAs in samples from several body sites of patients with exanthem subitum and their mothers by polymerase chain reaction assay. J. Med. Virol., 46, 52–55.CrossRefGoogle ScholarPubMed
Takahashi, Y., Yamada, M., Nakamura, J.et al. (1997). Transmission of human herpesvirus 7 through multigenerational families in the same household. Pediatr. Infect. Dis. J., 16, 975–978.CrossRefGoogle ScholarPubMed
Tanaka-Taya, K., Kondo, T., Mukai, T.et al. (1996). 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. J. Med. Virol., 48, 88–94.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Thawaranantha, D., Chimabutra, K., Balachandra, K.et al. (2002). Genetic variations of human herpesvirus 7 by analysis of glycoproteins B and H, and R2-repeat regions. J. Med. Virol., 66, 370–377.CrossRefGoogle ScholarPubMed
Torelli, G., Barozzi, P., Marasca, R.et al. (1995). Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of human peripheral blood mononuclear cells in vivo. J. Med. Virol., 46, 178–188.CrossRefGoogle Scholar
Loon, N. M., Gummuluru, S., Sherwood, D. J., Marentes, R., Hall, C. B., and Dewhurst (1995). Direct sequence analysis of human herpesvirus 6 (HHV-6) sequences from infants and comparison of HHV-6 sequences from mother/infant pairs. Clin. Infect. Dis., 21, 1017–1019.CrossRefGoogle ScholarPubMed
Ward, K. N., Leong, H. N., Nacheva, E. P.et al. (2006). Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles. J. Clin. Microbiol., 44, 1571–1574.CrossRefGoogle ScholarPubMed
Wilborn, F., Schmidt, C. A., Zimmermann, R., Brinkmann, V., Neipel, F., and Siegert, W. (1994). Detection of herpesvirus type 6 by polymerase chain reaction in blood donors: random tests and prospective longitudinal studies. Br. J. Haematol., 88, 187–192.CrossRefGoogle ScholarPubMed
Wilborn, F., Schmidt, C. A., Lorenz, F.et al. (1995). Human herpesvirus type 7 in blood donors: detection by the polymerase chain reaction. J. Med. Virol., 47, 65–69.CrossRefGoogle ScholarPubMed
Wyatt, L. S. and Frenkel, N. (1992). Human herpesvirus 7 is a constitutive inhabitant of adult human saliva. J. Virol., 66, 3206–3209.Google ScholarPubMed
Wyatt, L. S., Rodriguez, W. J., Balachandran, N., and Frenkel, N. (1991). Human herpesvirus 7: antigenic properties and prevalence in children and adults. J. Virol., 65, 6260–6265.Google ScholarPubMed
Yoshikawa, T., Asano, Y., Kobayashi, I.et al. (1993). Seroepidemiology of human herpesvirus 7 in healthy children and adults in Japan. J. Med. Virol., 41, 319–323.CrossRefGoogle ScholarPubMed
Yoshikawa, T., Ihira, M., Suzuki, K.et al. (2001). Primary human herpesvirus 6 infection in liver transplant recipients. J. Pediatr., 138, 921–925.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×