Possible chromosomal and germline integration of human herpesvirus 7

Publisher Copyright: © 2017 The Authors. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.Human herpesvirus 7 (HHV-7) is a betaherpesvirus, and is phylogenetically related to both HHV-6A and HHV-6B. The presence of telomeric repeat sequences at both ends of its genome should make it equally likely to integrate into the human telomere as HHV-6. However, numerous studies have failed to detect germline integration of HHV-7, suggesting an important difference between the HHV-6A/-6B and HHV-7 genomes. In search of possible germline integrated HHV-7, we developed a sensitive and quantitative real-time PCR assay and discovered that primers designed against some parts of the HHV-7 genome can frequently miss HHV-7 positive clinical samples even though they work efficiently in cell-culture-derived HHV-7 positive materials. Using a primer pair against the U90 ORF of HHV-7, we identified a possible case of germline integration of HHV-7 with one copy of viral genome per cell in both peripheral blood cells and hair follicles. Chromosomal integration of HHV-7 in these individuals was confirmed by fluorescence in situ hybridization analysis. Germline integration of HHV-7 was further confirmed by detection of ~2.6 copies of HHV-7 in the hair follicles of one of the parents. Our results shed light on the complex nature of the HHV-7 genome in human-derived materials in comparison to cell-culture-derived materials and show the need for stringent criteria in the selection of primers for epidemiological HHV-7 studies.Peer reviewe

Spectrum of Kaposi's Sarcoma-Associated Herpesvirus, or Human Herpesvirus 8, Diseases

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), discovered in 1994, is a human rhadinovirus (gamma-2 herpesvirus). Unlike other human herpesviruses (herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, HHV-6, and HHV-7), it is not widespread in the general population and has many unique proteins. HHV-8 is strongly associated with all subtypes of Kaposi's sarcoma (KS), multicentric Castleman's disease, and a rare form of B-cell lymphoma, primary effusion lymphoma. In addition, HHV-8 DNA sequences have been found in association with other diseases, but the role of the virus in these diseases is largely unconfirmed and remains controversial. The seroprevalence of HHV-8, based on detection of latent and lytic proteins, is 2 to 5% in healthy donors except in certain geographic areas where the virus is endemic, 80 to 95% in classic KS patients, and 40 to 50% in HIV-1 patients without KS. This virus can be transmitted both sexually and through body fluids (e.g., saliva and blood). HHV-8 is a transforming virus, as evidenced by its presence in human malignancies, by the in vitro transforming properties of several of its viral genes, and by its ability to transform some primary cells in culture. It is not, however, sufficient for transformation, and other cofactors such as immunosuppressive cytokines are involved in the development of HHV-8-associated malignancies. In this article, we review the biology, molecular virology, epidemiology, transmission, detection methods, pathogenesis, and antiviral therapy of this newly discovered human herpesvirus

Human herpesvirus type 8 in salivary gland tumors

Background: The new human herpesvirus type 8 (HHV-8) has been detected in all types of Kaposi's sarcomas, as well as in body-cavity lymphomas and Castleman's disease, furthermore molecular biologic studies have identified a number of potential viral oncogenes. There is evidence for sexual transmission of HHV-8 in HIV-seropositive patients, but the route of infection among the HIV-seronegative population is uncertain. Findings of HHV-8 DNA in saliva in some eases are suggestive of nonsexual transmission associated with latent infection of the salivary gland (as it is known for EBV, CMV, HHV-6 and HHV-7). Objective: As little is known about the etiological factors of salivary gland tumors and to give more insights into HHV-8 cell tropism normal salivary gland tissue (n = 12) and different salivary glands neoplasm (n = 58) were tested for HHV-8 sequences and antigens in HIV-seronegative patients. Study design: Biopsies of both normal salivary gland and tumors were investigated for HHV-8 sequences. A nested-PCR method was used for amplification of HHV-8 DNA fragments and the nature of the amplification products was confirmed by Southern blot hybridization. In addition, we used an in situ hybridization technique and immunohistochemical staining for detection of HHV-s infected cells. The sera of the respective patients were tested for anti-HHV-8 antibodies using commercial IFA and an ELISA-assay. Results: HHV-8 DNA sequences could be detected in one bilateral MALT-lymphoma of the parotid gland of a HHV-8 seropositive female patient suffering from Sjogren's syndrome (SS). The remaining parotid samples did neither show HHV-8 sequences nor HHV-s antigens. Using above assays only one additional patient was seropositive for HHV-8. Conclusion: Our data suggest that HHV-8 does not usually infect the salivary gland in HIV-seronegative patients and does not seem to play a pathogenic role in vascular and epithelial salivary gland neoplasm. Pathogenic role of HHV-8 in Sjogren's syndrome associated MALT-lymphoma remains unclear and should be subject of further studies. (C) 2000 Elsevier Science B.V. All rights reserved

Persistent Human Herpesvirus-6 Infection in Patients with an Inherited Form of the Virus

Human herpesvirus-6 (HHV-6)A and 6B are ubiquitous betaherpesviruses viruses with lymphotropic and neurotropic potential. As reported earlier, these viruses establish latency by integration into the telomeres of host chromosomes. Chromosomally integrated HHV-6 (CIHHV-6) can be transmitted vertically from parent to child. Some CIHHV-6 patients are suffering from neurological symptoms, while others remain asymptomatic. Four patients with CIHHV-6 and CNS dysfunction were treated with valganciclovir or foscarnet. HHV-6 replication was detected by reverse transcriptase polymerase chain reaction amplification of a late envelope glycoprotein. In this study we also compared the inherited and persistent HHV-6 viruses by DNA sequencing. The prevalence of CIHHV-6 in this cohort of adult patients from the USA suffering from a wide range of neurological symptoms including long-term fatigue were found significantly greater than the reported 0.8% in the general population. Long-term antiviral therapy inhibited HHV-6 replication as documented by loss of viral mRNA production. Sequence comparison of the mRNA and the inherited viral genome revealed that the transcript is produced by an exogenous virus. In conclusion, the data presented here document that some individuals with CIHHV-6 are infected persistently with exogenous HHV-6 strains that lead to a wide range of neurological symptoms; the proposed name for this condition is inherited herpesvirus 6 syndrome or IHS. J Med. Virol. 85:1940–1946, 2013. © 2013 Wiley Periodicals, Inc