Lymphoproliferative Syndromes Associated With Human Herpesvirus-6a and Human Herpesvirus-6b

Eliassen, Eva; Krueger, G. R. F.; Luppi, Mario; Ablashi, Dharam V.

doi:10.4084/mjhid.2018.035

Cited by 11 publications

(7 citation statements)

References 162 publications

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“…Only such combined efforts, including biopsy and autopsy studies, have allowed us to identify the causative roles of some herpesviruses in the individual patient. 69 – 72 …”

Section: Specific Entitiesmentioning

confidence: 99%

The Importance of the Autopsy in Medicine: Perspectives of Pathology Colleagues

et al. 2019

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This article presents a perspective on the importance of the autopsy in medical practice and science based on experiences of the authors as physician-scientists involved in autopsy practice. Our perspectives are presented on the seminal contributions of the autopsy in the areas of cardiovascular disease, including congenital heart disease, atherosclerosis, coronary artery disease, and myocardial infarction, and infectious disease, including tuberculosis and viral infections. On the positive side of the future of the autopsy, we discuss the tremendous opportunities for important research to be done by application of advanced molecular biological techniques to formalin-fixed, paraffin-embedded tissue blocks obtained at autopsy. We also note with concern the countervailing forces impacting the influence of pathology in education and clinical practice at our academic medical centers, which also present impediments to increasing autopsy rates. Our challenge as academic pathologists, whose careers have been molded by involvement in the autopsy, is to counter these trends. The challenges are great but the benefits for medicine and society are enormous.

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“…Only such combined efforts, including biopsy and autopsy studies, have allowed us to identify the causative roles of some herpesviruses in the individual patient. 69 – 72 …”

Section: Specific Entitiesmentioning

confidence: 99%

The Importance of the Autopsy in Medicine: Perspectives of Pathology Colleagues

et al. 2019

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“…Like other members of the herpesvirus family, HHV-6B establishes a lifelong latent infection (1). Reactivation of HHV-6B is associated with drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which is a life-threatening syndrome (7,8). Reactivation also occurs in patients with immunocompromised status and has been reported in 40% to 70% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) (6,9).…”

mentioning

confidence: 99%

Humanization of Murine Neutralizing Antibodies against Human Herpesvirus 6B

Wang

Nishimura

Maekawa

et al. 2019

J Virol

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Exanthem subitum is a common childhood illness caused by primary infection with human herpesvirus 6B (HHV-6B). It is occasionally complicated by febrile seizures and even encephalitis. HHV-6B reactivation also causes encephalitis, especially after allogeneic hematopoietic stem cell transplantation. However, no adequate antiviral treatment for HHV-6B has yet been established. Mouse-derived monoclonal antibodies (MAbs) against the HHV-6B envelope glycoprotein complex gH/gL/gQ1/gQ2 have been shown to neutralize the viral infection. These antibodies have the potential to become antiviral agents against HHV-6B despite their inherent immunogenicity to the human immune system. Humanization of MAbs derived from other species is one of the proven solutions to such a dilemma. In this study, we constructed chimeric forms of two neutralizing MAbs against HHV-6B to make humanized antibodies. Both showed neutralizing activities equivalent to those of their original forms. This is the first report of humanized antibodies against HHV-6B and provides a basis for the further development of HHV-6B-specific antivirals. IMPORTANCE Human herpesvirus 6B (HHV-6B) establishes lifelong latent infection in most individuals after the primary infection. Encephalitis is the most severe complication caused by both the primary infection and the reactivation of HHV-6B and is the cause of considerable mortality in patients, without any established treatments to date. The humanization of the murine neutralizing antibodies described in this research provided a feasible way to reduce the inherent immunogenicity of the antibodies without changing their neutralizing activities. These newly designed chimeric antibodies against HHV-6B have the potential to be candidates for antivirals for future use. a IC 50 , half-maximal inhibitory concentration. FIG 7 Model of the possible mechanisms of neutralization by MAbs KH-1 and OHV-3. For HHV-6B entry, the gH/gL/gQ1/gQ2 glycoprotein complex, especially gQ1, binds directly to the cell receptor CD134. (A) KH-1, which interacts with gQ1, could directly inhibit receptor binding. (B) The interaction of gH with OHV-3 could affect gH function (fusion or association with gB) and thus inhibit viral entry. Humanization of Neutralizing MAbs against HHV-6B Journal of Virology May 2019 Volume 93 Issue 10 e02270-18 jvi.asm.org 7proteins by MAbs may affect their functions for entry. Further studies are required to answer these questions. MATERIALS AND METHODS Cells and viruses.Human embryonic kidney (HEK) 293T cells were cultured at 37°C under 5% CO 2 in Dulbecco's modified Eagle medium (DMEM) containing 8% fetal bovine serum, 4 mM L-glutamine, and 20 g/ml gentamicin. Serum-free CD 293 medium (Thermo Fisher Scientific) supplemented with 4 mM L-glutamine and 20 g/ml gentamicin was used after transfections. The human T-cell line MT4 was cultured in RPMI 1640 medium with 8% fetal bovine serum containing 20 g/ml gentamicin. HHV-6B strain HST was prepared as described previously (15). For virus propagation, umbilical cord blood m...

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“…This high infection rate may be in part due to congenital transmission as HHV-6 has the ability to integrate into chromosomal DNA [9], thereby increasing the potential for reactivation in immunocompromised states [10,11]. Similarly, there are reports of HHV-6 reactivation in cancers such as lymphoma and leukemia [12][13][14]. Specific to the CNS, HHV-6 has been linked to variable detection in inheritable glial tumors, but there are no known reports relating HHV-6 and pilocytic astrocytoma [4,5,15,16].…”

Section: Discussionmentioning

confidence: 99%

Primary Human Herpes Virus-6 Causing Recalcitrant Pyrexia after Pilocytic Astrocytoma Resection

et al. 2023

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Introduction: Human Herpes Virus-6 (HHV-6) is a ubiquitous virus but can lead to deleterious clinical manifestations due to its predilection for the pediatric central nervous system. Despite significant literature describing its common clinical course, it is rarely considered as a causative agent in CSF pleocytosis in the setting of craniotomy and external ventricular drainage device. Identification of a primary HHV-6 infection allowed for timely treatment with an antiviral agent along with earlier discontinuation of antibiotic regimen and expedited placement of a ventriculoperitoneal shunt. Case Presentation: A two-year-old girl presented with 3 months of progressive gait disturbance and intranuclear ophthalmoplegia. Following craniotomy for removal of 4th ventricular pilocytic astrocytoma and decompression of hydrocephalus, she suffered a prolonged clinical course due to persistent fevers and worsening CSF leukocytosis despite multiple antibiotic regimens. The patient was admitted to the hospital during the COVID-19 pandemic and isolated with her parents in the intensive care unit with strict infection control measures. FilmArray Meningitis/Encephalitis (FAME) panel ultimately detected HHV-6. Clinical confirmation of HHV-6-induced meningitis was proposed given improvement in CSF leukocytosis and fever reduction following the initiation of antiviral medications. Pathologic analysis of brain tumor tissue failed to show HHV-6 genome positivity, suggesting a primary peripheral etiology of infection. Discussion/Conclusion: Here, we present the first known case of HHV-6 infection detected by FAME following intracranial tumor resection. We propose a modified algorithm for persistent fever of unknown origin which may decrease symptomatic sequelae, minimize additional procedures, and shorten length of ICU stay.

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Lymphoproliferative Syndromes Associated With Human Herpesvirus-6a and Human Herpesvirus-6b

Cited by 11 publications

References 162 publications

The Importance of the Autopsy in Medicine: Perspectives of Pathology Colleagues

The Importance of the Autopsy in Medicine: Perspectives of Pathology Colleagues

Humanization of Murine Neutralizing Antibodies against Human Herpesvirus 6B

Primary Human Herpes Virus-6 Causing Recalcitrant Pyrexia after Pilocytic Astrocytoma Resection

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