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human herpesvirus 6a ts suppresses both transformation by h-ras and transcription by the h-ras and human immunodeficiency virus type 1 promoters.human herpesvirus 6 strain u1102 (hhv-6a) was shown to contain a 1,473-bp functional transformation suppressor gene (ts). ts exhibited 24% identity and 51% similarity to adeno-associated virus type 2 rep68/78. like adeno-associated virus type 2 rep68/78, hhv-6a ts suppressed h-ras transformation of nih 3t3 cells. suppression of h-ras transformation was eliminated by translation termination linker mutation at amino acid 25, 125, or 245. these data indicated the importance of the c-terminal portio ...19957609062
cell lines containing and expressing the human herpesvirus 6a ts gene are protected from both h-ras and bpv-1 transformation.human herpesvirus 6a (hhv-6a) strain u1102 was previously shown to contain a 1473 bp transformation suppressor gene (ts) (araujo et al., 1995). ts inhibited transformation of nih3t3 cells by h-ras and transcription of the h-ras and human immunodeficiency type 1 (hiv-1) promoters in transient transfection experiments. in the current study, stable nih3t3 cell lines expressing ts protein were established by transfection with prc-ts containing the ts gene under the control of the rous sarcoma virus ...19979050993
genetic content of a 20.9 kb segment of human herpesvirus 6b strain z29 spanning the homologs of human herpesvirus 6a genes u40-57 and containing the origin of dna replication.a continuous 20.9 kb sequence from human herpesvirus 6 variant b (hhv-6b) strain z29 (genbank accession number l16947) is genetically colinear with a discrete segment of the human cytomegalovirus (hcmv) ul region and with hhv-6 variant a (hhv-6a). short nucleotide sequence determinations at multiple sites within an 8.5 kb region immediately 3' to the 20.9 kb contig revealed additional colinearity between hhv-6b, hcmv and hhv-6a. homology studies with the predicted peptide sequences from 11 compl ...19979155876
physical and genetic maps of the human herpesvirus 7 strain sb genome.human herpesvirus 7 (hhv-7) is a close relative of human herpesvirus 6a (hhv-6a) and human herpesvirus 6b (hhv-6b) based on limited biologic and genetic data. in this work we describe physical and genetic maps for hhv-7 strain sb [hhv-7(sb)], which was obtained from the saliva of a healthy adult. the hhv-7(sb) genome length is approximately 144 kb by clamped homogeneous electric field gel electrophoresis and approximately 135 kb by summation of restriction endonuclease fragments. we constructed ...19969526545
human herpesvirus 6b genome sequence: coding content and comparison with human herpesvirus 6a.human herpesvirus 6 variants a and b (hhv-6a and hhv-6b) are closely related viruses that can be readily distinguished by comparison of restriction endonuclease profiles and nucleotide sequences. the viruses are similar with respect to genomic and genetic organization, and their genomes cross-hybridize extensively, but they differ in biological and epidemiologic features. differences include infectivity of t-cell lines, patterns of reactivity with monoclonal antibodies, and disease associations. ...199910482553
complete dna sequence of the rat cytomegalovirus genome.we have determined the complete genome sequence of the maastricht strain of rat cytomegalovirus (rcmv). the rcmv genome has a length of 229,896 bp and is arranged as a single unique sequence flanked by 504-bp terminal direct repeats. rcmv was found to have counterparts of all but one of the open reading frames (orfs) that are conserved between murine cmv (mcmv) and human cmv (hcmv). like hcmv, rcmv lacks homologs of the genes belonging to the mcmv m02 glycoprotein gene family. however, rcmv cont ...200010906222
characterization of transcripts expressed from human herpesvirus 6a strain gs immediate-early region b u16-u17 open reading frames.several gene fragments of human herpesvirus 6 (hhv-6) have been shown to activate the human immunodeficiency virus (hiv) type 1 long terminal repeat (ltr). an open reading frame (orf) designated b701 (y. geng, b. chandran, s. f. josephs, and c. wood, j. virol. 66:1564-1570, 1992), found within a 22-kb hhv-6a strain gs [hhv-6a(gs)] genomic fragment and a 3.8-kb sali subfragment, was shown to activate the hiv ltr. b701, also known as hhv-6 u16, is located in the immediate-early b (ie-b) region of ...200011069999
human herpesvirus 6a dna is detected frequently in plasma but rarely in peripheral blood leukocytes of patients after bone marrow transplantation.a real-time quantitative polymerase chain reaction assay was devised to determine the load of human herpesvirus (hhv)-6a and -6b dna in paired samples of plasma and peripheral blood leukocytes (pbl) of 25 bone marrow transplant patients. the assay detects hhv-6 dna variants a and b in a linear range of 10(7)-10(1) genome equivalents per assay. viral dna was measured in 336 paired dna pbl samples and in corresponding plasma samples. hhv-6a and/or -6b dna was detected in pbl of 23 of 25 patients a ...200111076708
human herpesvirus 6 infection arrests cord blood mononuclear cells in g(2) phase of the cell cycle.we here report that after infection with human herpesvirus 6a, human cord blood mononuclear cells accumulate in g(2)/m phase of the cell cycle. experiments with foscarnet or ultraviolet (uv)-irradiated virus stocks pointed at an (immediate-)early, newly formed viral protein to be responsible for the arrest. at the molecular level, p53, cyclin b(1), cyclin a and tyrosine(15)-phosphorylated cdk1 accumulated after hhv-6a infection, indicating an arrest in g(2). however, no change was observed in th ...200414987992
the ul97 protein kinase of human cytomegalovirus and homologues in other herpesviruses: impact on virus and host.the human herpesviruses, herpes simplex virus 1 (hsv-1), hsv-2, varicella zoster virus (vzv), epstein-barr virus (ebv), human cytomegalovirus (hcmv), human herpesvirus 6a (hhv-6a), hhv-6b, hhv-7 and hhv-8, establish persistent infections with possible recurrence during immunosuppression. hcmv replication is inhibited by the nucleoside analogue ganciclovir (gcv), the compound of choice for the treatment of hcmv diseases and preemptive treatment of infections. the viral ul97 protein (pul97) which ...200415023359
use of a multi-virus array for the study of human viral and retroviral pathogens: gene expression studies and chip-chip analysis.since the discovery of human immunodeficiency virus (hiv-1) twenty years ago, aids has become one of the most studied diseases. a number of viruses have subsequently been identified to contribute to the pathogenesis of hiv and its opportunistic infections and cancers. therefore, a multi-virus array containing eight human viruses implicated in aids pathogenesis was developed and its efficacy in various applications was characterized.200415169557
dna microarrays for virus detection in cases of central nervous system infection.a low-density, high-resolution diagnostic dna microarray comprising 38 gene targets for 13 viral causes of meningitis and encephalitis was constructed. the array has been used for the detection of multiplex pcr-amplified viruses in cerebrospinal fluid (csf) and non-csf specimens. a total of 41 clinical specimens were positive for echoviruses (23 samples), herpes simplex virus type 2 (4 samples), varicella-zoster virus (4 samples), human herpesvirus 7 (1 sample), human herpesvirus 6a (1 sample) a ...200415583316
modulation of the cytokine network in human adult astrocytes by human herpesvirus-6a.human herpesvirus-6a (hhv-6a) is a common pathogen whose role in cns disorders including multiple sclerosis remains controversial. to understand how hhv-6a could influence inflammatory pathways in the cns, we infected cultured human adult astrocytes and examined the expression of 268 cytokines, chemokines, growth factors and their receptors by gene profiling. hhv-6 infection alone had little effect on the astrocyte gene profile but strongly altered the astrocyte response to proinflammatory cytok ...200515904975
u94 alters fn1 and angptl4 gene expression and inhibits tumorigenesis of prostate cancer cell line pc3.insensitivity of advanced-stage prostate cancer to androgen ablation therapy is a serious problem in clinical practice because it is associated with aggressive progression and poor prognosis. targeted therapeutic drug discovery efforts are thwarted by lack of adequate knowledge of gene(s) associated with prostate tumorigenesis. therefore there is the need for studies to provide leads to targeted intervention measures. here we propose that stable expression of u94, a tumor suppressor gene encoded ...200515972109
human herpesvirus 6a decreases the susceptibility of macrophages to r5 variants of human immunodeficiency virus 1: possible role of rantes and il-8.human herpesvirus 6 (hhv-6) frequently reactivates in human immunodeficiency virus 1 (hiv-1) infected patients, and is thought to be a cofactor in aids progression. macrophages are targets and reservoirs of hiv-1 and hhv-6; hence, they have an important role in dissemination and pathogenesis of these viruses. the present study examined the effects of hhv-6 a variant on replication of r5 variants of hiv-1 in macrophages. for this purpose, hiv-1 replication was investigated in macrophages infected ...200616815583
complexities in human herpesvirus-6a and -6b binding to host cells.human herpesvirus-6a and -6b uses the cellular receptor cd46 for fusion and infection of the host cell. the viral glycoprotein complex gh-gl from hhv-6a binds to the short consensus repeat 2 and 3 in cd46. although all the major isoforms of cd46 bind the virus, certain isoforms may have higher affinity than others for the virus. within recent years, elucidation of the viral complex has identified additional hhv-6a and -6b specific glycoproteins. thus, gh-gl associates with a gq1-gq2 dimer to for ...200616959284
complete replication cycle and acquisition of tegument in nucleus of human herpesvirus 6a in astrocytes and in t-cells.the ultrastructural replication cycle of human herpesvirus 6a and 6b, both t-lymphotropic viruses, with tropism for the central nervous system, was compared by electron microscopy in the same cells, that is, in the t-lymphoblastoid cell line supt-1 and in human astrocytes. both hhv-6a and hhv-6b replicated efficiently in supt-1 and formed viral particles. the tegument is the least characterized structure of the herpesviral particle and both variants were able to form intranuclear membrane compar ...200617063514
apoptotic effects of human herpesvirus-6a on glia and neurons as potential triggers for central nervous system autoimmunity.human herpesvirus type 6 (hhv-6a and/or hhv-6b) has been tentatively associated with multiple sclerosis (ms). however, there is currently no direct proof of pathogenicity.200617276360
human herpesvirus 6a accelerates aids progression in macaques.although hiv is the necessary and sufficient causative agent of aids, genetic and environmental factors markedly influence the pace of disease progression. clinical and experimental evidence suggests that human herpesvirus 6a (hhv-6a), a cytopathic t-lymphotropic dna virus, fosters the progression to aids in synergy with hiv-1. in this study, we investigated the effect of coinfection with hhv-6a on the progression of simian immunodeficiency virus (siv) disease in pig-tailed macaques (macaca neme ...200717360322
human herpesvirus-6a and -6b encode viral immunoevasins that downregulate class i mhc molecules.like all other members of the herpesvirus family, the closely related human herpesviruses-6 and -7 (hhv-6,7) persist in their host throughout life. in so doing, without exception, every member of the herpesvirus family has evolved mechanisms to avoid detection by the immune system. in particular, human cytomegalovirus (hcmv), mouse cytomegalovirus (mcmv), human herpesvirus-8 (hhv-8), and herpes simplex virus (hsv) all encode multiple proteins that interfere with proper mhc class i antigen presen ...200717467766
human herpesvirus 6a (hhv-6a) and hhv-6b alter e2f1/rb pathways and e2f1 localization and cause cell cycle arrest in infected t cells.e2f transcription factors play pivotal roles in controlling the expression of genes involved in cell viability as well as genes involved in cell death. e2f1 is an important constituent of this protein family, which thus far contains eight members. the interaction of e2f1 with its major regulator, retinoblastoma protein (rb), has been studied extensively in the past two decades, concentrating on the role of e2f1 in transcriptional regulation and the role of rb in cell replication and cancer forma ...200717913805
purification of infectious human herpesvirus 6a virions and association of host cell proteins.viruses that are incorporating host cell proteins might trigger autoimmune diseases. it is therefore of interest to identify possible host proteins associated with viruses, especially for enveloped viruses that have been suggested to play a role in autoimmune diseases, like human herpesvirus 6a (hhv-6a) in multiple sclerosis (ms).200717949490
human herpesvirus 6 (hhv-6) induces dysregulation of glutamate uptake and transporter expression in astrocytes.human herpesvirus 6 (hhv-6) infects and establishes latency in the central nervous system (cns). reactivation of latent hhv-6 has been associated with neurologic diseases including epilepsy and multiple sclerosis (ms). in vivo, hhv-6 has been localized to astrocytes and can infect human astrocytes in vitro, suggesting that this virus may have a tropism for glial cells and may affect glial cell function. an essential role of astrocytes in the cns is active maintenance of the excitatory neurotrans ...200818247129
immunomodulation by herpesvirus u51a chemokine receptor via ccl5 and fog-2 down-regulation plus xcr1 and ccr7 mimicry in human leukocytes.human herpesvirus-6a (hhv-6a) betachemokine-receptor u51a binds inflammatory modulators ccl2, ccl5, ccl11, ccl7, and ccl13. this unique specificity overlaps that of human chemokine receptors ccr1, ccr2, ccr3, and ccr5. in model cell lines, expression leads to ccl5 down-regulation with both constitutive and inducible signaling. here, immunomodulation pathways are investigated in human leukocytes permissive for infection. constitutive signaling was shown using inositol phosphate assays and inducib ...200818286574
recent developments in liver pathology.progress in liver histopathology continues to be made, as evidenced by recent publications in all areas of hepatobiliary disease. multinucleated giant hepatocytes, known to be associated with autoimmune and drug hepatitis, now have been seen in chronic hepatitis c with or without hiv infection and in patients with infection by human herpesvirus-6a. the new term mallory-denk body (formerly the mallory body) recognizes the substantial contributions to this field by professor helmut denk of austria ...200919289183
differential effect of human herpesvirus 6a on cell division and apoptosis among naive and central and effector memory cd4+ and cd8+ t-cell subsets.the immune responses of naive and different memory subsets of cd4(+) and cd8(+) t cells to human herpesvirus 6 (hhv-6) have not been previously investigated. we show that hhv-6a induces cell division, as measured by 5,6-carboxyfluorescein succinimidyl ester dye and flow cytometry, predominantly in two populations of effector memory cd4(+) and cd8(+) t cells (t(em) and t(emra)); naïve (t(n)) and central memory (t(cm)) cd4(+) and cd8(+) t cells showed almost no cell division. in contrast, hhv-6a i ...200919297473
evolution of siv toward rantes resistance in macaques rapidly progressing to aids upon coinfection with hhv-6a.progression to aids is often associated with the evolution of hiv-1 toward increased virulence and/or pathogenicity. evidence suggests that a virulence factor for hiv-1 is resistance to ccr5-binding chemokines, most notably rantes, which are believed to play a role in hiv-1 control in vivo. hiv-1 can achieve rantes resistance either by phenotypic switching from an exclusive ccr5 usage to an expanded coreceptor specificity, or by the acquisition of alternative modalities of ccr5 usage. an infecti ...200919573243
ccr5 signalling, but not darc or d6 regulatory, chemokine receptors are targeted by herpesvirus u83a chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway.abstract:200919643012
mhc2ta rs4774c and hhv-6a active replication in multiple sclerosis patients.in a previous report, a strong gene-environment interaction between human herpesvirus 6a (hhv6a) active replication and mhc2ta rs4774c was demonstrated. the objectives of this study were: (i) to reappraise the association that was found in the previous study; (ii) to evaluate if ms patients with minor allele c and hhv-6a active infection had different clinical behavior; and (iii) to analyze the possible association of mhc2ta rs4774c with epstein-barr virus (ebv).201019659749
direct repeat 6 from human herpesvirus-6b encodes a nuclear protein that forms a complex with the viral dna processivity factor p41.the sali-l fragment from human herpesvirus 6a (hhv-6a) encodes a protein dr7 that has been reported to produce fibrosarcomas when injected into nude mice, to transform nih3t3 cells, and to interact with and inhibit the function of p53. the homologous gene in hhv-6b is dr6. since p53 is deregulated in both hhv-6a and -6b, we characterized the expression of dr6 mrna and the localization of the translated protein during hhv-6b infection of hct116 cells. expression of mrna from dr6 was inhibited by ...200919829698
the u24 protein from human herpesvirus 6 and 7 affects endocytic recycling.modulation of t-cell receptor expression and signaling is essential to the survival of many viruses. the u24 protein expressed by human herpesvirus 6a, a ubiquitous human pathogen, has been previously shown to downregulate the t-cell receptor. here, we show that u24 also mediates cell surface downregulation of a canonical early endosomal recycling receptor, the transferrin receptor, indicating that this viral protein acts by blocking early endosomal recycling. we present evidence that u24 is a c ...201019923186
[establishment and clinical application of a new real time pcr assay for simultaneous detection of human herpesvirus-6a and human herpesvirus-6b].human herpesvirus 6 (hhv-6) isolates are classified into two variants, hhv-6a and hhv-6b, based on distinct genetic, antigenic and biological characteristics. hhv-6 has been associated with encephalitis in children recently. this study aimed to establish a real time pcr assay for simultaneous detection of the two subtypes of hhv-6, and apply this new assay to children with suspected encephalitis, then analyze the relationship between the infection with hhv-6 and encephalitis in children.200919951517
the dr1 and dr6 first exons of human herpesvirus 6a are not required for virus replication in culture and are deleted in virus stocks that replicate well in t-cell lines.human herpesvirus 6a (hhv-6a) and hhv-6b are lymphotropic viruses which replicate in cultured activated cord blood mononuclear cells (cbmcs) and in t-cell lines. viral genomes are composed of 143-kb unique (u) sequences flanked by approximately 8- to 10-kb left and right direct repeats, dr(l) and dr(r). we have recently cloned hhv-6a (u1102) into bacterial artificial chromosome (bac) vectors, employing dna replicative intermediates. surprisingly, hhv-6a bacs and their parental dnas were found to ...201020053742
direct detection of human herpesvirus 6 dna in serum by variant specific loop-mediated isothermal amplification in hematopoietic stem cell transplant recipients.a variant specific direct loop-mediated isothermal amplification (lamp) method was developed to detect human herpesvirus-6 (hhv-6) variants in serum samples. specific primers were designed against hhv-6 u86 gene. initial validation analysis confirmed high specificity and sensitivity of the method. this method was shown to be highly reliable for monitoring active hhv-6 infection in hematopoietic stem cell transplant recipients.201020138915
the latent human herpesvirus-6a genome specifically integrates in telomeres of human chromosomes in vivo and in vitro.previous research has suggested that human herpesvirus-6 (hhv-6) may integrate into host cell chromosomes and be vertically transmitted in the germ line, but the evidence--primarily fluorescence in situ hybridization (fish)--is indirect. we sought, first, to definitively test these two hypotheses. peripheral blood mononuclear cells (pbmcs) were isolated from families in which several members, including at least one parent and child, had unusually high copy numbers of hhv-6 dna per milliliter of ...201020212114
immediate–early viral gene regulation and functionbetaherpesviruses such as human cytomegalovirus (hcmv), human herpesvirus-6a and 6b (hhv-6), and human herpesvirus-7 (hhv-7) replicate more slowly than alphaherpesviruses, are highly species-specific for infection, and establish latency in progenitor cells of the bone marrow and monocytes of the blood. hcmv has been the prototype of the betaherpesviruses for studies of gene expression and regulation. in cell culture, hcmv strains have been adapted to preferentially infect ...200721348077
development of a microwell adapted immunoblot system with recombinant antigens for distinguishing human herpesvirus (hhv)6a and hhv6b and detection of human cytomegalovirus.abstract background: the human cytomegalovirus (hcmv) and the human herpesvirus 6 (hhv6) are widely distributed in the human population. the variants a and b of hhv6 are closely related to each other and cannot be distinguished by common serological methods like enzyme-linked immunosorbent assay (elisa) or immunofluorescence test (ift). the aim of this study was to develop a microwell-adapted blot system for specificity detection of human cytomegalovirus and human herpesvirus 6a and 6b (hhv6a, h ...201121756162
quantitation of human herpesvirus-6a, -6b and -7 dnas in whole blood, mononuclear and polymorphonuclear cell fractions from healthy blood donors.diagnosis of human herpesvirus-6a (hhv-6a), -6b (hhv-6b) or -7 (hhv-7) infections is often based on the measure of viral load in blood.201122133730
human herpesvirus 6a induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways.abstract:201122152093
development of a human herpesvirus 6 species-specific immunoblotting assay.in order to assess the full spectrum of human herpesvirus 6a (hhv-6a)- and hhv-6b-associated diseases, we sought to develop an hhv-6 species-specific serological assay based on immunoblot analysis. the immunodominant proteins encoded by open reading frame u11, p100 for hhv-6a (strain u1102) and 101k for hhv-6b (strain z29), were selected to generate virus species-specific antigens. recombinant p100 and 101k were produced in a prokaryotic expression system. the expression of these proteins was co ...201222278837
human herpesvirus 6a infects human embryonic fibroblasts and induces g2/m arrest and cell death.human herpesvirus 6 (hhv-6) is a beta-herpesvirus capable of infecting cells from different origin. in this study, infection with hhv-6a of human embryonic fibroblasts (hefs) was performed. infected cells showed obvious cytopathic effects (cpe). pcr and immunohistochemical tests also confirmed that hefs are susceptible to hhv-6a infection. the biological effects of hhv-6a infection on hefs were studied. infected cells showed decreased proliferation as measured by [(3)h] thymidine incorporation a ...201222337306
antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6a presenting with cognitive dysfunction.human herpesvirus 6 (hhv-6) is a neurotropic virus implicated in central nervous system (cns) dysfunction, multiple sclerosis, seizures and encephalitis. inherited or "chromosomally integrated" hhv-6 (cihhv-6) is a condition characterized by high dna loads and germ line transmission of hhv-6 genomes, which are integrated into the telomere.201222770640
vironome of kaposi sarcoma associated herpesvirus-inflammatory cytokine syndrome in an aids patient reveals co-infection of human herpesvirus 8 and human herpesvirus 6a.kshv inflammatory cytokine syndrome (kics) is a newly described condition characterized by systemic illness as a result of systemic, lytic kshv infection. we used illumina sequencing to establish the dna vironome of blood from such a patient. it identified concurrent high-level viremia of human herpesvirus (hhv) 8 and 6a. the hhv8 plasma viral load was 5,300,000 copies/ml, which is the highest reported to date; this despite less than five skin lesions and no hhv8 associated lymphoma. this is the ...201222925337
features of human herpesvirus-6a and -6b entry.human herpesvirus-6 (hhv-6) is a t lymphotropic herpesvirus belonging to the betaherpesvirinae subfamily. hhv-6 was long classified into variants a and b (hhv-6a and hhv-6b); however, recently, hhv-6a and hhv-6b were reclassified as different species. the process of herpesvirus entry into target cells is complicated, and in the case of hhv-6a and hhv-6b, the detailed mechanism remains to be elucidated, although both viruses are known to enter cells via endocytosis. in this paper, (1) findings ab ...201223133452
human herpesvirus-6a/b binds to spermatozoa acrosome and is the most prevalent herpesvirus in semen from sperm donors.an analysis of all known human herpesviruses has not previously been reported on sperm from normal donors. using an array-based detection method, we determined the cross-sectional frequency of human herpesviruses in semen from 198 danish sperm donors. fifty-five of the donors had at least one ejaculate that was positive for one or more human herpesvirus. of these 27.3% (n = 15) had a double herpesvirus infection. if corrected for the presence of multiple ejaculates from some donors, the adjusted ...201223144982
no serological evidence for a role of hhv-6 infection in chronic fatigue syndrome.human herpesvirus 6a (hhv-6a) and human herpesvirus 6b (hhv-6b) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases. here luciferase immunoprecipitation systems (lips) was used to develop hhv-6 serologic diagnostic tests using antigens encoded by the u11 gene from hhv-6a (p100) and hhv-6b (p101). analysis of the antibody responses against renilla luciferase fusions with different hhv-6b p101 fragments identified ...201223145212
novel marmoset (callithrix jacchus) model of human herpesvirus 6a and 6b infections: immunologic, virologic and radiologic characterization.human herpesvirus 6 (hhv-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. hhv-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the cns. animal models of hhv-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack cd46, the receptor for cellular entry. therefore, we investigated the effects of hhv-6 infections in a non-human p ...201323382677
human herpesvirus 6a partially suppresses functional properties of dc without viral replication.human herpesvirus 6a (hhv-6a) is a common virus with a worldwide distribution that has been associated with multiple sclerosis. whether hhv-6a can replicate in dendritic cells (dc) and how the infection might modulate the functional properties of the cell are currently not well known and need further investigations. here, we show that a non-productive infection of hhv-6a in dc leads to the up-regulation of hla-abc, via autocrine ifn-α signaling, as well as the up-regulation of hla-dr and cd86. h ...201323526966
complete genome sequences of elephant endotheliotropic herpesviruses 1a and 1b determined directly from fatal cases.a highly lethal hemorrhagic disease associated with infection by elephant endotheliotropic herpesvirus (eehv) poses a severe threat to asian elephant husbandry. we have used high-throughput methods to sequence the genomes of the two genotypes that are involved in most fatalities, namely, eehv1a and eehv1b (species elephantid herpesvirus 1, genus proboscivirus, subfamily betaherpesvirinae, family herpesviridae). the sequences were determined from postmortem tissue samples, despite the data contai ...201323552421
human herpesvirus 6a induces apoptosis of hsb-2 cells via a mitochondrion-related caspase pathway.apoptosis plays an important role in the pathogenesis of viral infections. in this study, we investigated the cell death processes during productive hhv-6a infection and the underlying mechanisms. annexin v-pi staining and electron microscopy indicated that hhv-6a is a strong inducer of apoptosis. hhv-6a infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria. the cell death was associated with activation of caspase-3 and cleavage of dna repair ...201023554661
identification of the human herpesvirus 6a gq1 domain essential for its functional conformation.human 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 essentia ...201323596294
mapping the telomere integrated genome of human herpesvirus 6a and 6b.human herpesvirus 6b (hhv-6b) is the causative agent of roseola infantum. hhv-6a and 6b can reactivate in immunosuppressed individuals and are linked with severe inflammatory response, organ rejection and central nervous system diseases. about 0.85% of the us and uk population carries an integrated hhv-6 genome in all nucleated cells through germline transmission. we have previously reported that the hhv-6a genome integrated in telomeres of patients suffering from neurological dysfunction and al ...201323648233
cd134 is a cellular receptor specific for human herpesvirus-6b entry.human herpesvirus-6b (hhv-6b) is a t lymphotropic β-herpesvirus that is clearly distinct from human herpesvirus-6a (hhv-6a) according to molecular biological features. the international committee on taxonomy of viruses recently classified hhv-6b as a separate species. the primary hhv-6b infection causes exanthem subitum and is sometimes associated with severe encephalopathy. more than 90% of the general population is infected with hhv-6b during childhood, and the virus remains throughout life as ...201323674671
complete genome sequence of early passaged human herpesvirus 6a (gs strain) isolated from north america.the genome sequence of the original human herpesvirus 6a (hhv-6a) (gs isolate) has never been determined. dna from a very low passage (<5 times) hhv-6a gs stock was isolated and sequenced, making it the first hhv-6a of u.s. origin to be fully sequenced. such a sequence will be helpful for comparative analysis with other hhv-6a strains, including the u1102 strain isolated from uganda.201323766398
human herpesvirus 6a infection and immunopathogenesis in humanized rag2⁻/⁻ γc⁻/⁻ mice.although serious human diseases have been correlated with human herpesvirus 6a (hhv-6a) and hhv-6b, the lack of animal models has prevented studies which would more definitively link these viral infections to disease. hhv-6a and hhv-6b have recently been classified as two distinct viruses, and in this study we focused specifically on developing an in vivo model for hhv-6a. here we show that rag2⁻/⁻γc⁻/⁻ mice humanized with cord blood-derived human hematopoietic stem cells produce human t cells t ...201324006442
immunomodulation and immunosuppression by human herpesvirus 6a and 6b.like other members of the herpesviridae family, human herpesvirus (hhv)-6a and hhv-6b have developed a wide variety of strategies to modulate or suppress host immune responses and, thereby, facilitate their own spread and persistence in vivo. long considered two variants of the same virus, hhv-6a and hhv-6b have recently been reclassified as distinct viral species, although the established nomenclature has been maintained. in this review, we summarize the distinctive profiles of interaction of t ...201324163703
human herpesvirus-6a gq1 and gq2 are critical for human cd46 usage.based on genetic and antigenic differences and on their cell tropism, human herpes virus-6 (hhv-6) has been classified into two variants, hhv-6a and hhv-6b. recently, these variants were re-classified as two different species. the hhv-6a glycoprotein complex, gh/gl/gq1/gq2 binds to its cellular receptor, cd46; however, the corresponding complex in hhv-6b rarely binds to cd46. to determine which viral molecules in the glycoprotein complex determine hhv-6a-cd46 binding, each molecule of the hhv-6a ...201424215487
mhc class i molecules are incorporated into human herpesvirus-6 viral particles and released into the extracellular environment.human herpesvirus-6 (hhv-6), which belongs to the betaherpesvirus subfamily, mainly replicates in t lymphocytes. here, we show that mhc class i molecules are incorporated into hhv-6 viral particles and released into the extracellular environment. in addition, hhv-6a/b-infected t cells showed reduced surface and intracellular expression of mhc class i molecules. the cellular machinery responsible for molecular transport appears to be modified upon hhv-6 infection, causing mhc class i molecules to ...201424330265
human herpesvirus 6 (hhv-6) alters e2f1/rb pathways and utilizes the e2f1 transcription factor to express viral genes.e2f transcription factors play pivotal roles in controlling the expression of genes involved in cell-cycle progression. different viruses affect e2f1/retinoblastoma (rb) interactions by diverse mechanisms releasing e2f1 from its suppressor rb, enabling viral replication. we show that in t cells infected with human herpesvirus 6a (hhv-6a), the e2f1 protein and its cofactor dp1 increased, whereas the rb protein underwent massive degradation without hyperphosphorylation at three sites known to cont ...201424335704
characterization of the human herpesvirus 6a u23 gene.human herpesvirus 6 (hhv-6), which replicates abundantly in t cells, belongs to the roseolovirus genus within the betaherpesvirus subfamily. members of the roseolovirus genus encode seven unique genes, u20, u21, u23, u24, u24a, u26, and u100. the present study focused on one of these, u23, by analyzing the characteristics of its gene product in hhv-6a-infected cells. the results indicated that the u23 protein was expressed at the late phase of infection as a glycoprotein, but was not incorporate ...201424503071
human herpesvirus 6a infection in cd46 transgenic mice: viral persistence in the brain and increased production of proinflammatory chemokines via toll-like receptor 9.human herpesvirus 6 (hhv-6) is widely spread in the human population and has been associated with several neuroinflammatory diseases, including multiple sclerosis. to develop a small-animal model of hhv-6 infection, we analyzed the susceptibility of several lines of transgenic mice expressing human cd46, identified as a receptor for hhv-6. we showed that hhv-6a (gs) infection results in the expression of viral transcripts in primary brain glial cultures from cd46-expressing mice, while hhv-6b (z ...201424574405
molecular and virological evidence of viral activation from chromosomally integrated human herpesvirus 6a in a patient with x-linked severe combined immunodeficiency.it has been unclear whether chromosomally integrated human herpesvirus 6 (cihhv-6) can be activated with pathogenic effects on the human body. we present molecular and virological evidence of cihhv-6a activation in a patient with x-linked severe combined immunodeficiency. these findings have significant implications for the management of patients with cihhv-6.201424803376
detailed study of the interaction between human herpesvirus 6b glycoprotein complex and its cellular receptor, human cd134.recently, we identified a novel receptor, cd134, which interacts with the human herpesvirus 6b (hhv-6b) glycoprotein (g)h/gl/gq1/gq2 complex and plays a key role in the entry of hhv-6b into target cells. however, details of the interaction between the hhv-6b gh/gl/gq1/gq2 complex and cd134 were unknown. in this study, we identified a cysteine-rich domain (crd), cdr2, of cd134 that is critical for binding to the hhv-6b glycoprotein complex and hhv-6b infection. furthermore, we found that the expr ...201425008928
genomic organization and molecular characterization of porcine cytomegalovirus.a strain of the porcine cytomegalovirus (pcmv), which causes inclusion body rhinitis in newborn piglets, has been characterized with respect to its complete genome sequence. the virus genome is 128,367bp, containing 79 predicted open reading frames (orfs). of these orfs, 69 have counterparts in human herpesvirus 6a (hhv-6a), 6b (hhv-6b) and 7 (hhv-7), and two orfs are homologous to other members in the subfamily betaherpesvirinae. eight orfs have no homologs in herpesvirus. homologs had higher i ...201425010282
prevalence of human herpesvirus 6a and 6b during pregnancy.the aim of the present study was to assess the frequency of human herpesvirus 6a (hhv-6a) and human herpesvirus 6b (hhv-6b) infection during pregnancy. 100-100 blood samples were collected from pregnant and non-pregnant women, then nucleic acid was isolated from both plasma and leukocytes fraction. nested and real-time pcr were used to detect and differentiate hhv-6a and hhv-6b dna and to determine viral loads. reverse transcription pcr (rt-pcr) for hhv-6 u79/80 mrna was performed in order to re ...201425102917
anti-human herpesvirus 6a/b igg correlates with relapses and progression in multiple sclerosis.to analyze the titers of the igg and igm antibodies against human herpesvirus 6a/b (hhv-6a/b) in multiple sclerosis (ms) patients treated with different disease modified therapies (dmts) along two-years of follow-up.201425110949
inhibition of interleukin-2 gene expression by human herpesvirus 6b u54 tegument protein.human herpesvirus 6b (hhv-6b) is a ubiquitous pathogen causing lifelong infections in approximately 95% of humans worldwide. to persist within its host, hhv-6b has developed several immune evasion mechanisms, such as latency, during which minimal proteins are expressed, and the ability to disturb innate and adaptive immune responses. the primary cellular targets of hhv-6b are cd4(+) t cells. previous studies by flamand et al. (l. flamand, j. gosselin, i. stefanescu, d. ablashi, and j. menezes, b ...201425122797
roseoloviruses in transplant recipients: clinical consequences and prospects for treatment and prevention trials.roseoloviruses frequently reactivate in transplant recipients. we review the impact of roseoloviruses in transplant recipients and highlight research priorities. human herpesvirus 6a (hhv-6a) and hhv-6b were recently classified as distinct species with important differences. both viruses can result in inherited chromosomally integrated hhv-6, which may cause complications after transplant. hhv-6b is the primary species associated with disease and appears to have pleiotropic effects on the centra ...201425285614
human herpesviruses-encoded dutpases: a family of proteins that modulate dendritic cell function and innate immunity.we have previously shown that epstein-barr virus (ebv)-encoded dutpase can modulate innate immune responses through the activation of tlr2 and nf-κb signaling. however, whether this novel immune function of the dutpase is specific for ebv or a common property of the herpesviridae family is not known. in this study, we demonstrate that the purified viral dutpases encoded by herpes simplex virus type 2 (hsv-2), human herpesvirus-6a (hhv-6a), human herpesvirus-8 (hhv-8) and varicella-zoster virus ( ...201425309527
analyses of germline, chromosomally integrated human herpesvirus 6a and b genomes indicate emergent infection and new inflammatory mediators.human herpesvirus-6a (hhv-6a) is rarer than hhv-6b in many infant populations. however, they are similarly prevalent as germline, chromosomally integrated genomes (cihhv-6a/b). this integrated form affects 0.1-1 % of the human population, where potentially virus gene expression could be in every cell, although virus relationships and health effects are not clear. in a czech/german patient cohort cihhv-6a was more common and diverse than cihhv-6b. quantitative pcr, nucleotide sequencing and telom ...201525355130
germ-line transmitted, chromosomally integrated hhv-6 and classical hodgkin lymphoma.a unique feature of both human herpesvirus 6a and b (hhv-6a and b) among human herpesviruses is their ability to integrate into chromosomal telomeres. in some individuals integrated viral genomes are present in the germ-line and result in the vertical transmission of hhv-6; however, little is known about the disease associations of germ-line transmitted, chromosomally integrated hhv-6 (cihhv-6). recent publications suggest that hhv-6 is associated with classical hodgkin lymphoma (chl). here we e ...201425384040
clinical impact of primary infection with roseoloviruses.the roseoloviruses, human herpesvirus-6a -6b and -7 (hhv-6a, hhv-6b and hhv-7) cause acute infection, establish latency, and in the case of hhv-6a and hhv-6b, whole virus can integrate into the host chromosome. primary infection with hhv-6b occurs in nearly all children and was first linked to the clinical syndrome roseola infantum. however, roseolovirus infection results in a spectrum of clinical disease, ranging from asymptomatic infection to acute febrile illnesses with severe neurologic comp ...201425462439
recent developments in animal models for human herpesvirus 6a and 6b.progress in the identification of suitable animal models for human herpesvirus (hhv)-6a and hhv-6b infections has been slow. recently, new models have been established, mainly for hhv-6a, which reproduce some pathological features seen in humans. neuroinflammatory signs were observed in infected marmosets and cd46-transgenic mice; although viral replication was not prominent, persistence of viral dna and specific immunologic responses were detected, suggesting an immune-mediated pathogenic mecha ...201425462440
gp96 interacts with hhv-6 during viral entry and directs it for cellular degradation.cd46 and cd134 mediate attachment of human herpesvirus 6a (hhv-6a) and hhv-6b to host cell, respectively. but many cell types interfere with viral infection through rapid degradation of viral dna. hence, not all cells expressing these receptors are permissive to hhv-6 dna replication and production of infective virions suggesting the involvement of additional factors that influence hhv-6 propagation. here, we used a proteomics approach to identify other host cell proteins necessary for hhv-6 bin ...201425470779
a human herpesvirus 6a-encoded microrna: role in viral lytic replication.human herpesvirus 6a (hhv-6a), a member of the betaherpesvirus family, is associated with several human diseases. like all herpesviruses, hhv-6a establishes a lifelong, latent infection in its host. reactivation of hhv-6a is frequent within the immunosuppressed and immunocompromised populations and results in lytic viral replication within multiple organs, often leading to severe disease. micrornas (mirnas) are key regulators of multiple cellular processes that regulate the translation of specif ...201525520507
complete genome sequence of the human herpesvirus 6a strain aj from africa resembles strain gs from north america.the genome sequence of human herpesvirus 6a (hhv-6a) strain aj was determined in a comparison of target enrichment and long-range pcr using next-generation sequencing methodologies. the analyses show 85 predicted open reading frames (orfs), conservation with sequenced hhv-6a reference strain u1102, and closest identity to the recently determined gs strain, despite different geographic origins (united states and gambia).201525676750
maturation of human herpesvirus 6a glycoprotein o requires coexpression of glycoprotein h and glycoprotein l.glycoprotein o (go) is conserved among betaherpesviruses, but little is known about the maturation process of go in human herpesvirus 6 (hhv-6). we found that hhv-6 go maturation was accompanied by cleavage of its carboxyl terminus and required coexpression of gh and gl, which promoted the export of go out of the endoplasmic reticulum (er). finally, we also found that go was not required for hhv-6a growth in t cells.201525694589
modulatory effects on dendritic cells by human herpesvirus 6.human herpesvirus 6a and 6b are β-herpesviruses approaching 100% seroprevalance worldwide. these viruses are involved in several clinical syndromes and have important immunomodulatory effects. dendritic cells (dc) are key players in innate and adaptive immunity. accordingly, dc are implicated in the pathogenesis of many human diseases, including infections. in this review the effects of hhv-6 infection on dc will be discussed.201525983728
characterization of human herpesvirus 6a/b u94 as atpase, helicase, exonuclease and dna-binding proteins.human herpesvirus-6a (hhv-6a) and hhv-6b integrate their genomes into the telomeres of human chromosomes, however, the mechanisms leading to integration remain unknown. hhv-6a/b encode a protein that has been proposed to be involved in integration termed u94, an ortholog of adeno-associated virus type 2 (aav-2) rep68 integrase. in this report, we addressed whether purified recombinant maltose-binding protein (mbp)-u94 fusion proteins of hhv-6a/b possess biological functions compatible with viral ...201525999342
acute human herpesvirus-6a infection of human mesothelial cells modulates hla molecules.human herpesvirus 6a (hhv-6a) causes ubiquitous infections and has been associated with several diseases in immunosuppressed and immune dysregulated individuals. although considered a lymphotropic virus, hhv-6a has the potential to infect many cell types, inducing important alterations in the infected cell. in our search for additional potential targets for hhv-6a infection, we analyzed the susceptibility of human mesothelial cells to viral infection. hhv-6a infection was performed and analyzed ...201526085284
human herpesvirus 6a u14 is important for virus maturation.human herpesvirus 6a (hhv-6a) u14 is a virion protein with little known function in virus propagation. here, we elucidated its function by constructing and analyzing u14-mutated viruses. we found that u14 is essential for hhv-6a propagation. we then constructed a mutant virus harboring dysfunctional u14. this virus showed severely reduced growth and retarded maturation. taken together, these data indicate that u14 plays an important role during hhv-6a maturation.201526559847
complete genome sequence of germline chromosomally integrated human herpesvirus 6a and analyses integration sites define a new human endogenous virus with potential to reactivate as an emerging infection.human herpesvirus-6a and b (hhv-6a, hhv-6b) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "cihhv-6a/b". these affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. we previously showed that cihhv-6a was more divergent than cihhv-6b by examining four genes in 44 european cihhv-6a/b cardiac/haematology patients. there was evidence for gene expression/reactivation, implying functio ...201626784220
cycling probe-based real-time pcr for the detection of human herpesvirus 6a and b.human herpesvirus 6 (hhv-6) is classified as two distinct species: hhv-6a and b. hhv-6b infection can cause several clinical manifestations in transplant recipients including encephalitis, bone marrow suppression, and pneumonitis. in contrast to hhv-6b, the clinical features of hhv-6a infection remain largely undefined. herein, we developed a multiplex cycling probe real-time pcr that discriminated between hhv-6a and hhv-6b. the assay was hhv-6-specific and no cross amplification was demonstrate ...201626945690
hhv-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus-6a from the telomere of chromosome 19q.primary effusion lymphomas (pel) are associated with human herpesvirus-8 (hhv-8) and usually occur in immunocompromised individuals. however, there are numerous reports of hhv-8-unrelated pel-like lymphomas with unknown aetiology. here we characterize an hhv-8-unrelated pel-like lymphoma in an elderly woman who was negative for human immunodeficiency viruses 1 and 2, and hepatitis b and c. the woman was, however, a carrier of an inherited-chromosomally-integrated human herpesvirus-6a (icihhv-6a) ...201626947392
complete unique genome sequence, expression profile, and salivary gland tissue tropism of the herpesvirus 7 homolog in pigtailed macaques.human herpesvirus 6a (hhv-6a), hhv-6b, and hhv-7 are classified as roseoloviruses and are highly prevalent in the human population. roseolovirus reactivation in an immunocompromised host can cause severe pathologies. while the pathogenic potential of hhv-7 is unclear, it can reactivate hhv-6 from latency and thus contributes to severe pathological conditions associated with hhv-6. because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological ...201627170755
the telomeric repeats of human herpesvirus 6a (hhv-6a) are required for efficient virus integration.human herpesvirus 6a (hhv-6a) and 6b (hhv-6b) are ubiquitous betaherpesviruses that infects humans within the first years of life and establishes latency in various cell types. both viruses can integrate their genomes into telomeres of host chromosomes in latently infected cells. the molecular mechanism of viral integration remains elusive. intriguingly, hhv-6a, hhv-6b and several other herpesviruses harbor arrays of telomeric repeats (tmr) identical to human telomere sequences at the ends of th ...201627244446
hhv-6a in vitro infection of thyrocytes and t cells alters the expression of mirna associated to autoimmune thyroiditis.human herpesviruses have been hypothesized as environmental triggers in the development of autoimmune thyroid diseases (aitd), and in particular active human herpesvirus 6a (hhv-6a) infection was detected in thyrocytes of hashimoto's thyroiditis (ht) patients, who also show specific anti-viral immune responses. on the other hand, aitd patients display modulation of specific mirnas in thyroid tissue and blood. we wanted to ascertain whether hhv-6a infection might be correlated to the mirna dysreg ...201728081700
a murine herpesvirus closely related to ubiquitous human herpesviruses causes t-cell depletion.mouse models of human herpesvirus infections the human roseoloviruses hhv6a, hhv6b, and hhv7 comprise the roseolovirus genus of the human betaherpesvirinae subfamily. infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology because they are nearly ubiquitous and display species-specific tropism. furthermore, controlled study of infection has been hampered by the lack of experim ...201728179532
human herpesvirus 6a (hhv-6a) exhibits restrictive propagation with limited activation of pkr-eif2α stress pathway.the eif2α protein plays a critical role in the regulation of translation. the production of dsrna during viral replication can activate protein kinase r (pkr) which phosphorylates the eif2α, leading to inhibition of the initial step of translation. many viruses have evolved gene products targeting pkr-eif2a pathway, indicating its importance in antiviral defense. in the present study we focus on alternations of pkr-eif2a pathway along hhv-6a infection while monitoring viral gene expression and i ...201728202752
chromosomal integration of hhv-6a during non-productive viral infection.human herpesvirus 6a (hhv-6a) and 6b (hhv-6b) are two different species of betaherpesviruses that integrate into sub-telomeric ends of human chromosomes, for which different prevalence rates of integration have been reported. it has been demonstrated that integrated viral genome is stable and is fully retained. however, study of chromosomally integrated viral genome in individuals carrying inherited hhv-6 (icihhv-6) showed unexpected number of viral dr copies. hence, we created an in vitro infec ...201728360414
cell culture systems to study human herpesvirus 6a/b chromosomal integration.human herpesviruses 6a/b (hhv-6a/b) can integrate their viral genomes in the telomeres of human chromosomes. the viral and cellular factors contributing to hhv-6a/b integration remain largely unknown, mostly due to the lack of efficient and reproducible cell culture models to study hhv-6a/b integration. in this study, we characterized the hhv-6a/b integration efficiencies in several human cell lines using two different approaches. first, after a short-term infection (5 h), cells were processed f ...201728468878
stabilization of telomere g-quadruplexes interferes with human herpesvirus 6a chromosomal integration.human herpesviruses 6a and 6b (hhv-6a/b) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. to achieve a better understanding of the hhv-6a/b integration mechanism, we made use of braco-19, a compound that stabilizes g-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. first, we analyzed the folding of telomeric sequences into g-quadruplex structures and their binding to braco-19 using g-q ...201728468887
purification, crystallization and x-ray diffraction study of the c-terminal domain of human herpesvirus 6a immediate early protein 2.human herpesvirus 6a (hhv-6a) starts its replication cycle following the action of immediate early proteins that transactivate viral promoters. immediate early protein 2 (ie2) of hhv-6a is a 1500 amino acid polypeptide with a c-terminal region that is conserved among beta-herpesvirus subfamily members. in this study, a structural domain in the homologous c-terminal region was subjected to secondary structure prediction, and residues 1324-1500 were subsequently designated as the c-terminal domain ...201728490711
expression of the human herpesvirus 6a latency-associated transcript u94a disrupts human oligodendrocyte progenitor migration.progression of demyelinating diseases is caused by an imbalance of two opposing processes: persistent destruction of myelin and myelin repair by differentiating oligodendrocyte progenitor cells (opcs). repair that cannot keep pace with destruction results in progressive loss of myelin. viral infections have long been suspected to be involved in these processes but their specific role remains elusive. here we describe a novel mechanism by which hhv-6a, a member of the human herpesvirus family, ma ...201728638124
hhv-6a/b integration and the pathogenesis associated with the reactivation of chromosomally integrated hhv-6a/b.unlike other human herpesviruses, human herpesvirus 6a and 6b (hhv-6a/b) infection can lead to integration of the viral genome in human chromosomes. when integration occurs in germinal cells, the integrated hhv-6a/b genome can be transmitted to 50% of descendants. such individuals, carrying one copy of the hhv-6a/b genome in every cell, are referred to as having inherited chromosomally-integrated hhv-6a/b (icihhv-6) and represent approximately 1% of the world's population. interestingly, hhv-6a/ ...201728672870
chromosomally integrated human herpesvirus 6: models of viral genome release from the telomere and impacts on human health.human herpesvirus 6a and 6b, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. the chromosomally integrated forms, cihhv-6a and cihhv-6b, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. the first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various mod ...201728704957
latency, integration, and reactivation of human herpesvirus-6.human herpesvirus-6a (hhv-6a) and human herpesvirus-6b (hhv-6b) are two closely related viruses that infect t-cells. both hhv-6a and hhv-6b possess telomere-like repeats at the terminal regions of their genomes that facilitate latency by integration into the host telomeres, rather than by episome formation. in about 1% of the human population, human herpes virus-6 (hhv-6) integration into germline cells allows the viral genome to be passed down from one generation to the other; this condition is ...201728737715
crystal structure of the dna-binding domain of human herpesvirus 6a immediate early protein 2.immediate early proteins of human herpesvirus 6a (hhv-6a) are expressed at the outset of lytic infection, and thereby regulate viral gene expression. immediate early protein 2 (ie2) of hhv-6a is a trans-activator that drives a variety of promoters. the c-terminal region of hhv-6a ie2 is shared among ie2 homologs in beta-herpesviruses, and is involved in dimerization, dna binding, and transcription factor binding. in this study, the structure of the c-terminal domain (ie2-ctd) was determined by x ...201728794035
inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres.the genomes of human herpesviruses 6a and 6b (hhv-6a and hhv-6b) have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. about 1% of people worldwide are carriers of chromosomally integrated hhv-6 (cihhv-6), which is inherited as a genetic trait. understanding the consequences of integration for the evolution of the viral genome, for the telomere and for the risk of disease associated with carrier status is hampered by ...201728835501
presence of human herpesvirus 6b in the pancreas of subjects with and without type 1 diabetes.the aims of this study were to investigate the presence of human herpesvirus 6 (hhv6) a and b in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (t1d).201728930865
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