Human betaherpesvirus 7 explained

Human betaherpesvirus 7
Field:Infectious disease

Human betaherpesvirus 7 (HHV-7) is one of nine known members of the Herpesviridae family that infects humans. HHV-7 is a member of Betaherpesvirinae, a subfamily of the Herpesviridae that also includes HHV-6 and Cytomegalovirus (HHV-5 or HCMV).[1] [2] HHV-7 often acts together with HHV-6, and the viruses together are sometimes referred to by their genus, Roseolovirus.[3] HHV-7 was first isolated in 1990 from CD4+ T cells taken from peripheral blood lymphocytes.[4]

Signs and symptoms

Both HHV-6B and HHV-7, as well as other viruses, can cause a skin condition in infants known as exanthema subitum, although HHV-7 causes the disease less frequently than HHV-6B.[5] HHV-7 infection also leads to or is associated with a number of other symptoms, including acute febrile respiratory disease, fever, rash, vomiting, diarrhea, low lymphocyte counts,[6] and febrile seizures,[7] though most often no symptoms present at all.

There are indications that HHV-7 can contribute to the development of drug-induced hypersensitivity syndrome (DIHS),[8] encephalopathy,[9] hemiconvulsion-hemiplegia-epilepsy syndrome,[10] hepatitis infection,[11] postinfectious myeloradiculoneuropathy,[12] pityriasis rosea,[13] and the reactivation of HHV-4, leading to "mononucleosis-like illness".[14] Drug reaction with eosinophilia and systemic symptoms (DRESS) is a specific type of DIHS that may be linked to HHV-7 as the condition may develop in response to herpesvirus antigens. In one study, 76% of the 40 examined patients with DRESS exhibited some reactivation of Epstein-Barr virus, HHV-6, or HHV-7. Additionally, HHV-7 is currently suspected as a causative agent of lichen planus. In one dermatologic study, 33 skin biopsies were performed and HHV-7 was found at higher rates in lichen planus lesions. Remission of lichen planus was also associated with lower levels of HHV-7.[15] HHV-7 was also detected in 79.3% of cervical tissue examined, indicating that sexual contact may be a route of transmission for HHV-7.[16]

Notably, HHV-7 and HHV-6 were detected in 56.3% of unspecified encephalopathy cases examined, with more HHV-7 positive cells in the gray matter of the frontal and temporal lobes HHV-7 is typically present in astrocytes and oligodendrocytes in the cerebral cortex, deep nuclei, and cerebellum.[17] HHV-7 infection, along with HSV1, VZV, and HHV6, was associated with increased risk of dementia.[18] However, further research is needed further elucidate the causative and correlative factors between HHV-7 and encephalopathy.

Complications with HHV-7 infection has been shown to be a factor in a great variety of transplant types. Specifically, HHV-7 infection has been linked to a reactivation of cytomegalovirus (CMV) infection in renal transplant patients and may be linked to graft-vs-host disease.

Virology

Structure

A mature virus particle measures about 170nm in diameter.[19]

The genome of HHV-7 is very similar to that of HHV-6, although it is about 10% smaller,[20] with a DNA genome of about 145,000 base pairs.[21] There are a number of key differences between the genome of HHV-7 and that of HHV-6, but the importance of them for viral DNA replication is not yet known.

Additionally, the HHV-7 virion appears to share much structural similarity to the HHV-6 virion. Despite this, some morphological characteristics of the viruses differ.

Cellular effects

HHV-7 resides mostly in CD4+ T cells,[22] albeit only in certain strains of them.[23] [24] [25] To enter CD4+ T cells, HHV-7, unlike HHV-6, uses CD4 and possibly some cell-surface glycoproteins to enter CD4+ T cells.[26] Despite this, HHV-7 may be able to enter cells that do not express the CD46 receptor. About a week after HHV-7 has infected a cell, it begins to downregulate CD4 transcription,[27] which interferes with HIV-1 infection[28] but may reactivate HHV-6 infection.[29] It is however unclear exactly what effect HHV-7 has on HIV infection.

There has been some inquiry into the relationship between HHV-7 and HIV-1 co-receptors CXCR4 and CCR5. During infection, HHV-7 causes a loss of CXCR4 in CD4+ T-cells in addition to lowering intracellular Ca2+ flux and chemotaxis in response to stroll cell-derived factor 1 (SDF-1). Additionally, a CXCR4 antagonist that was effective against HIV was shown to be ineffective at inhibiting HHV-7. This information indicates that CXCR4 and CCR5 are not essential receptor proteins for HHV-7 infection.

The trademark indication of HHV-7 infection at the cellular level is the presence of aforementioned syncytia. It is thought that these cells form via polyploidization resulting from a dysregulation of cyclin dependent kinase cdc2 and cyclin B. Giant cells form when the cell cycle is disrupted and accumulate between the G2 and M phase. However, syncytia formation is more complex than initially thought. Some research has shown that syncytia formation in betaherpesviruses can vary based on the type of envelop protein expressed by the virion as well as the particular type of cell that the virus is infecting.[30]

HHV-7 also notably activates IL-15 upon infection. Activation of IL-15 leads to an increased natural killer (NK) cell response. This is thought to be one of the immune system's main methods of responding to HHV-7 infection.

HHV-7 also has a number of other effects on cells. Among these include membrane leaking, the presence of lytic syncytia,[31] [32] occasional apoptosis,[33] the supporting of latent infection,[34] and increases and decreases in levels of certain cytokines.[35] [36]

Entry

HHV-7, like many other herpesviruses, relies on glycoproteins for entry. Specifically, HHV-7 is known to encode glycoproteins B, H, and L, but not C or D. In terms of betaherpesvirus specifically, it is thought that gB, gH, and gL are required for infection. Additionally, HHV-7 encodes a glycoprotein complex (gp82-105) that is unique to HHV-7 and HHV-6.[37]

Detection and treatment

In adults, the effects of HHV-7 separate from HHV-6 have not been well-researched.[1] One reason for this is because the detection of HHV-7 was at first difficult to do quickly, as the process for doing so involves a procedure that is difficult to do in commercial laboratories and because viral isolation and serological testing are long processes that do not lend themselves to finishing quickly. HHV-7 can be grown in various lymphocytes in vitro, but researchers have noted that the virus does not propagate well under laboratory conditions.[38] A process known as loop-mediated isothermal amplification (LAMP) has recently been applied to speed up detection of HHV-7, although a larger sample size of patients must be tested first to see if the test will still work across a broad range of subjects.[39] No reliable serological test has been developed yet for HHV-7 alone, but multiple are in the process of being developed. The use of PCR assays to test for HHV-7 is also being explored.[40]

No HHV-7 infection-specific treatment exists. While HHV-7 may not be linked to any specific diseases, some researchers emphasize that the virus is still clinically relevant as it causes significant complications in immunocompromised patients. Specific treatment options for HHV-6, 7, and 8 are currently in the early stages of development. Some research suggests that acyclovir and anti-CMV drugs such as cidofovir and foscarnet may have some therapeutic benefit in HHV-7 infection. Additionally, some experimental drugs, such as cyclotriazadisulfonamide, and 9-R-2-phosphonomethoxypropyladenine may be effective against HHV-7. There is a need for HHV-7 specific treatments, however, because broad-spectrum antivirals are typically toxic and thus unsuitable for prophylactic use.

Epidemiology

Over 95% of adults have been infected and are immune to HHV-7,[41] and over three quarters of those were infected before the age of six.[42] Primary infection of HHV-7 among children generally occurs between the ages of 2 and 5, which means it occurs after primary infection of HHV-6.[43] A 2014 Washington University School of Medicine's analysis of 102 healthy adults sampled at as many as five major body habitats found that HHV-7 was present in 98% of them, especially in the mouth.[44] A 2017 study looking at the human blood virome in 8,240 humans between the ages of 2 months to 102 years found that 20.37% of them were positive for HHV-7.[45]

Further reading

Notes and References

  1. Other Herpesviruses: HHV-6, HHV-7, HHV-8, HSV-1 and -2, VZV. American Journal of Transplantation. 4. 2004. Suppl 10 . 15504215. 10.1111/j.1600-6135.2004.00697.x. 66–71. free.
  2. 10.1017/S0950268899002599. Development of a PCR system for porcine cytomegalovirus detection and determination of the putative partial sequence of its DNA polymerase gene. 2810741. Epidemiology and Infection. 10487654. August 1999. 123. 1. 177–180. B. F.. Widen. J. P.. Lowings. S.. Belak. M.. Banks.
  3. Ongrádi. JóZsef. Kövesdi. Valéria. Kováts. Enikő. Orvosi Hetilap. Az emberi 7-es herpeszvírus. 151. 16. 645–51. 10.1556/OH.2010.28856. 2010. 20353917. hu. free.
  4. 10.1073/pnas.87.2.748. Frenkel. N. Schirmer. EC. Wyatt. LS. Katsafanas. G. Roffman. E. Danovich. RM. June. CH. Isolation of a new herpesvirus from human CD4+ T cells. Proceedings of the National Academy of Sciences of the United States of America. 87. 2. 748–52. 1990. 2153965. 53343. 1990PNAS...87..748F . free.
  5. Cohen. J. I.. Fahle. G.. Kemp. M. A.. Apakupakul. K.. Margolis. T. P.. Human Herpesvirus 6-A, 6-B and 7 in Vitreous Fluid Samples. Journal of Medical Virology. 82. 6. 996–9. 2010. 20419813. 2938775. 10.1002/jmv.21751.
  6. 10.1542/peds.99.3.e4. Suga. S. Yoshikawa. T. Nagai. T. Asano. Y. Clinical features and virological findings in children with primary human herpesvirus 7 infection. Pediatrics. 99. 3. E4. 1997. 9099769. free.
  7. 10.1136/adc.77.1.42. Clark. DA. Kidd. IM. Collingham. KE. Tarlow. M. Ayeni. T. Riordan. A. Griffiths. PD. Emery. VC. Pillay. D. Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction. Archives of Disease in Childhood. 77. 1. 1997. 9279150. 1717251. 42–5.
  8. Hara. H. Kobayashi. M. Yokoyama. A. Tochigi. M. Matsunaga. A. Shimizu. H. Goshima. J. Suzuki. H. Drug-induced hypersensitivity syndrome due to carbamazepine associated with reactivation of human herpesvirus 7. Dermatology. 211. 2. 159–61. 2005. 16088166. 10.1159/000086449. 41829848.
  9. Van Den Berg. JS. Van Zeijl. JH. Rotteveel. JJ. Melchers. WJ. Gabreëls. FJ. Galama. JM. Neuroinvasion by human herpesvirus type 7 in a case of exanthem subitum with severe neurologic manifestations. Neurology. 52. 5. 1077–9. 1999. 10102435. 10.1212/wnl.52.5.1077. 32547148.
  10. Kawada. J. Kimura. H. Yoshikawa. T. Ihira. M. Okumura. A. Morishima. T. Hayakawa. F. Hemiconvulsion-hemiplegia syndrome and primary human herpesvirus 7 infection. Brain & Development. 26. 6. 412–4. 2004. 15275707. 10.1016/j.braindev.2003.12.003. 21552203.
  11. Hashida. T. Komura. E. Yoshida. M. Otsuka. T. Hibi. S. Imashuku. S. Imashuku. S. Ishizaki. T. Yamada. A. Suga. S. Hepatitis in Association With Human Herpesvirus-7 Infection. Pediatrics. 96. 4 Pt 1. 783–785. 1995. 10.1542/peds.96.4.783. 7567349. 8.
  12. Mihara. T. Mutoh. T. Yoshikawa. T. Yano. S. Asano. Y. Yamamoto. H. Postinfectious myeloradiculoneuropathy with cranial nerve involvements associated with human herpesvirus 7 infection. Archives of Neurology. 62. 11. 1755–7. 2005. 16286551. 10.1001/archneur.62.11.1755. free.
  13. 10.1017/S0950268804002304. Chuh. A. Chan. H. Zawar. V. Pityriasis rosea--evidence for and against an infectious aetiology. Epidemiology and Infection. 132. 3. 381–390. 2004. 15188706. 2870116.
  14. Chiu. H-H. Lee. C-Y. Lee. P-I. Lin. K-H. Huang. L-M. Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection. Archives of Disease in Childhood. 78. 5. 479–480. 1998. 9659100. 1717555. 10.1136/adc.78.5.479.
  15. Wolz . Michael M. . Sciallis . Gabriel F. . Pittelkow . Mark R. . 2012-10-01 . Human Herpesviruses 6, 7, and 8 From a Dermatologic Perspective . Mayo Clinic Proceedings . English . 87 . 10 . 1004–1014 . 10.1016/j.mayocp.2012.04.010 . 0025-6196 . 3538396 . 22819486.
  16. Biganzoli . Patricia . Frutos . María Celia . Venezuela . Fernando . Mosmann . Jessica . Kiguen . Ana . Pavan . Jorge . Ferreyra . Leonardo . Cuffini . Cecilia . January 2020 . Detection of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) DNA in endocervical samples from a positive and negative HPV woman of Córdoba, Argentina . Journal of Clinical Pathology . en . 73 . 1 . 30–34 . 10.1136/jclinpath-2019-205795 . 31315894 . 197542736 . 0021-9746.
  17. Skuja . Sandra . Svirskis . Simons . Murovska . Modra . 2021-02-27 . Human Herpesvirus-6 and -7 in the Brain Microenvironment of Persons with Neurological Pathology and Healthy People . International Journal of Molecular Sciences . en . 22 . 5 . 2364 . 10.3390/ijms22052364 . 1422-0067 . 7956495 . 33673426 . free .
  18. Mekli . Krisztina . Lophatananon . Artitaya . Cant . Rachel . Burns . Alistair . Dobson . Curtis B. . Itzhaki . Ruth F. . Muir . Kenneth R. . 2022-10-12 . van de Vijver . David A. M. C. . Investigation of the association between the antibody responses to neurotropic viruses and dementia outcomes in the UK Biobank . PLOS ONE . en . 17 . 10 . e0274872 . 10.1371/journal.pone.0274872 . 1932-6203 . 9555633 . 36223333 . 2022PLoSO..1774872M . free .
  19. Klussmann. J. P.. Krueger. E.. Sloots. T.. Berneman. Z.. Arnold. G.. Krueger. G. R. F.. Ultrastructural study of human herpesvirus-7 replication in tissue culture. Virchows Archiv. 430. 5. 417–426. 1997. 9174632. 10.1007/s004280050051. 23966153.
  20. Determination and analysis of the complete nucleotide sequence of human herpesvirus 7. Nicholas. John. September 1996. Journal of Virology. 70. 9. 5975–5989. 8709220. 190618. 10.1128/JVI.70.9.5975-5989.1996.
  21. Web site: Human herpesvirus 7 infection. UpToDate. Tremblay. Cecile. Hirsch. Martin S. McGovern. Barbara H. 21 September 2020.
  22. 10.1073/pnas.93.18.9788. Katsafanas. Proceedings of the National Academy of Sciences of the United States of America. 93. 18. GC. Schirmer. 9788–92. EC. Wyatt. LS. Frenkel. N. In vitro activation of human herpesviruses 6 and 7 from latency. 1996. 8790409. 38507. 1996PNAS...93.9788K . free.
  23. 10.1073/pnas.89.21.10552. Berneman. ZN. Ablashi. DV. Li. G. Eger-Fletcher. M. Reitz Jr. MS. Hung. CL. Brus. I. Komaroff. AL. Gallo. RC. Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus. Proceedings of the National Academy of Sciences of the United States of America. 89. 21. 10552–10556. 1992. 1332051. 50377. 1992PNAS...8910552B. free.
  24. Mirandola. P. Secchiero. P. Pierpaoli. S. Visani. G. Zamai. L. Vitale. M. Capitani. S. Zauli. G. Infection of CD34(+) hematopoietic progenitor cells by human herpesvirus 7 (HHV-7). Blood. 96. 1. 126–131. 2000. 10891440. 10.1182/blood.V96.1.126.
  25. Yasukawa. M. Inoue. Y. Ohminami. H. Sada. E. Miyake. K. Tohyama. T. Shimada. T. Fujita. S. Human herpesvirus 7 infection of lymphoid and myeloid cell lines transduced with an adenovirus vector containing the CD4 gene. Journal of Virology. 71. 2. 1708–1712. 1997. 8995705. 191236. 10.1128/JVI.71.2.1708-1712.1997.
  26. 9151851. Secchiero. 1997. P. 4571–80. 6. Sun. 71. D. Journal of Virology. De Vico. AL. Crowley. RW. Reitz Jr. MS. Zauli. G. Lusso. P. Gallo. RC. Role of the extracellular domain of human herpesvirus 7 glycoprotein B in virus binding to cell surface heparan sulfate proteoglycans. 191679. 10.1128/JVI.71.6.4571-4580.1997.
  27. Hall. Annals of Internal Medicine. CB. 127. 6. 481–3. Human Herpesviruses at Sixes, Sevens, and More (editorial). 1997. 9313006. 10.7326/0003-4819-127-6-199709150-00010. 10.1.1.365.5033. 9448355.
  28. 10.1073/pnas.91.9.3872. Lusso. 43684. P. Secchiero. P. Crowley. RW. Garzino-Demo. A. Berneman. ZN. Gallo. RC. CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus. Proceedings of the National Academy of Sciences of the United States of America. 91. 9. 3872–6. 1994. 7909607. 1994PNAS...91.3872L . free.
  29. Tanaka-Taya. K. Kondo. T. Nakagawa. N. Inagi. R. Miyoshi. H. Sunagawa. T. Okada. S. Yamanishi. K. Reactivation of human herpesvirus 6 by infection of human herpesvirus 7. Journal of Medical Virology. 60. 3. 284–9. 2000. 10630960. 10.1002/(SICI)1096-9071(200003)60:3<284::AID-JMV6>3.0.CO;2-8. 42600320.
  30. Tang . Jiajia . Frascaroli . Giada . Zhou . Xuan . Knickmann . Jan . Brune . Wolfram . 2021-09-30 . Cell Fusion and Syncytium Formation in Betaherpesvirus Infection . Viruses . en . 13 . 10 . 1973 . 10.3390/v13101973 . 1999-4915 . 8537622 . 34696402 . free .
  31. Secchiero. P. Berneman. ZN. Gallo. RC. Lusso. P. Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test. Virology. 202. 1. 506–12. 1994. 8009865. 10.1006/viro.1994.1371.
  32. 10.1073/pnas.87.2.748. Frenkel. N. Schirmer. EC. Wyatt. LS. Katsafanas. G. Roffman. E. Danovich. RM. June. CH. Isolation of a new herpesvirus from human CD4+ T cells. Proceedings of the National Academy of Sciences of the United States of America. 87. 2. 748–52. 1990. 2153965. 53343. 1990PNAS...87..748F . free.
  33. Secchiero. P. Flamand. L. Gibellini. D. Falcieri. E. Robuffo. I. Capitani. S. Gallo. RC. Zauli. G. Human Herpesvirus 7 induces CD4(+) T-cell death by two distinct mechanisms: necrotic lysis in productively infected cells and apoptosis in uninfected or nonproductively infected cells. Blood. 90. 11. 4502–12. 1997. 9373261.
  34. Menegazzi. P. Galvan. M. Rotola. A. Ravaioli. T. Gonelli. A. Cassai. E. Di Luca. D. Temporal mapping of transcripts in human herpesvirus-7. Journal of General Virology. 80. 10. 2705–12. 1999. 10573164. 10.1099/0022-1317-80-10-2705. free.
  35. Atedzoe. BN. J. Menezes. M. D'Addario. J. Xu. J. Ongradi. A. Ahmad. Modulatory effects of human herpes virus-7 on cytokine synthesis and cell proliferation in human peripheral blood mononuclear cell cultures. Journal of Leukocyte Biology. 66. 5. 822–8. 1999. 10577515. 10.1002/jlb.66.5.822. free.
  36. Atedzoe. BN. Ahmad. A. Menezes. J. Enhancement of natural killer cell cytotoxicity by the human herpesvirus-7 via IL-15 induction. Journal of Immunology. 159. 10. 4966–72. 1997. 10.4049/jimmunol.159.10.4966 . 9366423. 42369655 . free.
  37. Skrincosky . David . Hocknell . Peter . Whetter . Linda . Secchiero . Paola . Chandran . Bala . Dewhurst . Stephen . 2000-05-15 . Identification and Analysis of a Novel Heparin-Binding Glycoprotein Encoded by Human Herpesvirus 7 . Journal of Virology . en . 74 . 10 . 4530–4540 . 10.1128/JVI.74.10.4530-4540.2000 . 0022-538X . 111973 . 10775589.
  38. Kempf . Werner . 2002-08-01 . Human Herpesvirus 7 in Dermatology . American Journal of Clinical Dermatology . en . 3 . 5 . 309–315 . 10.2165/00128071-200203050-00002 . 12069636 . 28402208 . 1179-1888.
  39. Detection of Human Herpesvirus 7 DNA by Loop-Mediated Isothermal Amplification. March 2004. Journal of Clinical Microbiology. 356854. Tetsushi. Yoshikawa. Masaru. Ihira. Shiho. Akimoto. Chie. Usui. Fumi. Miyake. Sadao. Suga. Yoshihiko. Enomoto. Ryota. Suzuki. Yukihiro . Asano. Y.. Nishiyama. 10.1128/JCM.42.3.1348-1352.2004. 42. 3. 1348–1352. 15004116. 8.
  40. Clark. D. A. Kidd. I M.. Collingham. K. E. Tarlow. M.. Ayeni. T.. Riordan. A.. Griffiths. P. D. Emery. V. C. Pillay. D.. Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction. Archives of Disease in Childhood. 77. 1. 42–45. 1997. 9279150. 1717251. 10.1136/adc.77.1.42.
  41. Clark. DA. Freeland. ML. MacKie. LK. Jarrett. RF. Onions. DE. Prevalence of antibody to human herpesvirus 7 by age. The Journal of Infectious Diseases. 168. 1. 251–2. 1993. 8390545. 10.1093/infdis/168.1.251.
  42. Cermelli. C. Fabio. G. Montorsi. M. Sabbatini. AM. Portolani. M. Prevalence of antibodies to human herpesviruses 6 and 7 in early infancy and age at primary infection. New Microbiologica. 19. 1. 1–8. 1996. 8673847.
  43. 10.1034/j.1399-3046.2003.02094.x. Yoshikawa. T. Human Herpesvirus-6 and -7 Infections in Transplantation. Pediatric Transplantation. 7. 1. 11–17. 2003. 12581322. 32279697.
  44. Wylie. Kristine M.. Mihindukulasuriya. Kathie A.. Zhou. Yanjiao. Sodergren. Erica. Storch. Gregory A.. Weinstock. George M.. 2014-01-01. Metagenomic analysis of double-stranded DNA viruses in healthy adults. BMC Biology. 12. 71. 10.1186/s12915-014-0071-7. 1741-7007. 4177058. 25212266 . free .
  45. Moustafa. Ahmed. Xie. Chao. Kirkness. Ewen. Biggs. William. Wong. Emily. Turpaz. Yaron. Bloom. Kenneth. Delwart. Eric. Nelson. Karen E.. 2017-03-22. The blood DNA virome in 8,000 humans. PLOS Pathogens. 13. 3. e1006292. 10.1371/journal.ppat.1006292. 28328962. 5378407. 1553-7374 . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Human betaherpesvirus 7".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.