Human herpesvirus 6: report of emerging pathogen in five patients with HIV/AIDS and review of the literature

Corti, Marcelo; Villafañe, María F.; Trione, Norberto; Mamanna, Lilia; Bouzas, Belén

doi:10.1590/s0037-86822011000400026

Cited by 12 publications

(16 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HHV-6B is a highly prevalent beta-herpes virus, infecting about 90% of the individuals in many Western populations [1]. The occurrence of episodes of viral reactivation observed in immunosuppressed individuals such as transplant patients and human immunodeficiency virus (HIV)-1-infected individuals [5][6][7][8][9]. Both CD4 and CD8 T cells responding to HHV-6B have been observed [10][11][12][13], although a full understanding of the role of the different subsets in controlling the infection is still lacking.…”

Section: Introductionmentioning

confidence: 99%

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

et al. 2019

View full text Add to dashboard Cite

Human herpes virus 6B (HHV‐6B) is a widespread virus that infects most people early in infancy and establishes a chronic life‐long infection with periodic reactivation. CD4 T cells have been implicated in control of HHV‐6B, but antigenic targets and functional characteristics of the CD4 T‐cell response are poorly understood. We identified 25 naturally processed MHC‐II peptides, derived from six different HHV‐6B proteins, and showed that they were recognized by CD4 T‐cell responses in HLA‐matched donors. The peptides were identified by mass spectrometry after elution from HLA‐DR molecules isolated from HHV‐6B‐infected T cells. The peptides showed strong binding to matched HLA alleles and elicited recall T‐cell responses in vitro. T‐cell lines expanded in vitro were used for functional characterization of the response. Responding cells were mainly CD3+CD4+, produced IFN‐γ, TNF‐α, and low levels of IL‐2, alone or in combination, highlighting the presence of polyfunctional T cells in the overall response. Many of the responding cells mobilized CD107a, stored granzyme B, and mediated specific killing of peptide‐pulsed target cells. These results highlight a potential role for polyfunctional cytotoxic CD4 T cells in the long‐term control of HHV‐6B infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Single, simultaneous, or consecutive reactivation also elicits debilitating conditions with involving CNS diseases (Holden and Vas 2007 ; Lautenschläger and Razonable 2012 ). HHV-6 species are able to transactivate heterologous viruses, especially HIV (Corti et al 2011 ; Ongrádi et al 2011 ) and human endogenous retroviruses (HERVs; Tai et al 2009 ; Turcanova et al 2009 ), which cause brain damage. Reactivation of HHV-6 in patients with AIDS can result in encephalitis or meningoencephalitis (Knox et al 1995 ).…”

Section: Introductionmentioning

confidence: 99%

Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals

et al. 2016

View full text Add to dashboard Cite

The roseoloviruses, human herpesvirus (HHV)-6A, HHV-6B, and HHV-7, can cause severe encephalitis or encephalopathy. In immunocompetent children, primary HHV-6B infection is occasionally accompanied by diverse clinical forms of encephalitis. Roseolovirus coinfections with heterologous viruses and delayed primary HHV-7 infection in immunocompetent adults result in very severe neurological and generalized symptoms. Recovery from neurological sequelae is slow and sometimes incomplete. In immunocompromised patients with underlying hematological malignancies and transplantation, frequent single or simultaneous reactivation of roseoloviruses elicit severe, lethal organ dysfunctions, including damages in the limbic system, brain stem, and hippocampus. Most cases have been due to HHV-6B with HHV-6A accounting for 2–3%. The most severe manifestation of HHV-6B reactivation is post-transplantation limbic encephalitis. Seizures, cognitive problems, and abnormal EEG are common. Major risk factors for HHV-6B-associated encephalitis include unrelated cord blood cell transplantation and repeated hematopoietic stem cell transplantation. Rare genetic disorders, male gender, certain HLA constellation, and immune tolerance to replicating HHV-6 in persons carrying chromosomally integrated HHV-6 might also predispose an individual to roseolovirus-associated brain damage. At this time, little is known about the risk factors for HHV-7-associated encephalitis. Intrathecal glial cell destruction due to virus replication, overexpression of proinflammatory cytokines, and viral mimicry of chemokines all contribute to brain dysfunction. High virus load in the cerebrospinal fluid, hippocampal astrogliosis, and viral protein expression in HHV-6B-associated cases and multiple microscopic neuronal degeneration in HHV-7-associated cases are typical laboratory findings. Early empirical therapy with ganciclovir or foscarnet might save the life of a patient with roseolovirus-associated encephalitis.

show abstract

“…Both variants can infect the brain, but HHV-6A is thought to be more neurotropic than HHV-6B (17). Several reports have shown that the reactivation of HHV-6A and -B may contribute to several diseases in immunosuppressed patients (18)(19)(20).…”

mentioning

confidence: 99%

Identification of the Human Herpesvirus 6A gQ1 Domain Essential for Its Functional Conformation

Maeki

Hayashi

Kawabata

et al. 2013

J Virol

View full text Add to dashboard Cite

cHuman herpesvirus 6 is a T lymphotropic herpesvirus, long classified into variants A and B (HHV-6A and HHV-6B) based on differences in sequence and pathogenicity. Recently, however, HHV-6A and HHV-6B were reclassified as different species. Here, we isolated a neutralizing monoclonal antibody (Mab) named AgQ 1-1 that was specific for HHV-6A glycoprotein Q1 (AgQ1), and we showed that amino acid residues 494 to 497 of AgQ1 were critical for its recognition by this Mab. This region was also essential for AgQ1's complex formation with gH, gL, and gQ2, which might be important for viral binding to the cellular receptor, CD46. In addition, amino acid residues 494 to 497 are essential for viral replication. Interestingly, this sequence corresponds to the domain on HHV-6B gQ1 that is critical for recognition by an HHV-6B-specific neutralizing Mab. Within this domain, only Q at position 496 of HHV-6A is distinct from the HHV-6B sequence; however, the mutant AgQ1(Q496E) was still clearly recognized by the Mab AgQ 1-1. Surprisingly, replacement of the adjacent amino acid, in mutant AgQ1(C495A), resulted in poor recognition by Mab AgQ 1-1, and AgQ1(C495A) could not form the gH/gL/gQ1/gQ2 complex. Furthermore, the binding ability of mutant AgQ1(L494A) with CD46 decreased, although it could form the gH/gL/gQ1/gQ2 complex and it showed clear reactivity to Mab AgQ 1-1. These data indicated that amino acid residues 494 to 497 of AgQ1 were critical for the recognition by Mab AgQ 1-1 and essential for AgQ1's functional conformation.

show abstract

Human herpesvirus 6: report of emerging pathogen in five patients with HIV/AIDS and review of the literature

Cited by 12 publications

References 7 publications

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals

Identification of the Human Herpesvirus 6A gQ1 Domain Essential for Its Functional Conformation

Contact Info

Product

Resources

About