Significance Based on several studies, including ours, we estimate that 40–70 million individuals carry a chromosomally integrated copy of the human herpesvirus 6 (HHV-6) genome in every cell their body. This condition is referred to as inherited HHV-6 (iciHHV-6). The regions targeted for integration are telomeres, which play important roles self-renewal capacity cells. Whether iciHHV-6 associated with disease remains unknown. After conducting population screen ( n = 20,000), our results...

The majority of human herpesvirus 6 (HHV-6) congenital infections (86%) originate from germ line transmission chromosomally integrated HHV-6 (ciHHV-6). To determine whether transplacentally acquired could derive the reactivated maternal ciHHV-6, we identified mother-infant pairs in which infants had proven and mothers documented sequenced compared gB gene sequences for each pair. Our data indicate that sequence found cord blood specimen was identical to corresponding mother but divergent...

Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are ubiquitous betaherpesviruses that infects humans within the first years of life establishes latency in various cell types. Both viruses can integrate their genomes into telomeres host chromosomes latently infected cells. The molecular mechanism viral integration remains elusive. Intriguingly, HHV-6A, HHV-6B several other herpesviruses harbor arrays telomeric repeats (TMR) identical to human telomere sequences at ends genomes. HHV-6A two TMR...

COVID-19 is associated with robust inflammation and partially impaired antiviral responses. The modulation of inflammatory gene expression by SARS-CoV-2 not completely understood. In this study, we characterized the responses mounted during infection. K18-hACE2 mice were infected a Wuhan-like strain SARS-CoV-2, transcriptional translational interferons (IFNs), cytokines, chemokines analyzed in mouse lung homogenates. Our results show that infection induces several pro-inflammatory CC CXC...

ABSTRACT Human herpesvirus 6 (HHV-6) is a ubiquitous virus with which infections have been associated pathologies ranging from delayed bone marrow engraftment to variety of neurological diseases. The lack standardized assay that can be used detect and estimate HHV-6 DNA contents in various clinical specimens lead has led discordant results among investigators on the potential association To identify most reliable sensitive assays, an identical set 11 coded serum samples spiked quantities...

Epidemiological investigations consistently demonstrate an overrepresentation of the elderly in COVID-19 hospitalizations and fatalities, making advanced age as a major predictor disease severity. Despite this, comprehensive understanding cellular molecular mechanisms explaining how old represents risk factor remain elusive. To investigate we compared SARS-CoV-2 infection outcomes young adults (2 months) geriatric (15–22 mice. Both groups K18-ACE2 mice were intranasally infected with 500...

Platelets, known for maintaining blood balance, also participate in antimicrobial defense. Upon severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, platelets become hyperactivated, releasing molecules such as cytokines, granule contents, and bioactive lipids. The key effector biolipids produced by include 12-hydroxyeicosatetraenoic acid (12-HETE) 12-hydroxyeicosatrienoic (12-HETrE), 12-lipoxygenase (12-LOX), prostaglandins thromboxane, cyclooxygenase-1. While prostaglandin...

ABSTRACT Human herpesviruses (HHV) are stealth pathogens possessing several decoy or immune system evasion mechanisms favoring their persistence within the infected host. Of these viruses, HHV-6 is among most successful human parasites, establishing lifelong infections in nearly 100% of individuals around world. To better understand this host-pathogen relationship, we determined whether could interfere with development innate antiviral response by affecting interferon (IFN) biosynthesis....

Two distinct human herpesvirus 6 (HHV-6) variants infect humans. HHV-6B is the etiologic agent of roseola and associated with life-threatening neurological diseases, such as encephalitis, well organ transplant failure. The epidemiology disease association for HHV-6A remain ill-defined. Specific anti-HHV-6 drugs do not exist classic antiherpes have secondary effects that are often problematic patients. Clinical trials using IFN were also performed inconclusive results. We investigated...

There is increasing evidence of a role for Toll-like receptors (TLRs) in inflammatory arthritis. The extra domain A (ED-A)-containing isoform fibronectin generated under pathologic conditions such as rheumatoid arthritis, and ED-A has been identified an endogenous TLR-4 ligand. Leukotriene B4 (LTB4) polymorphonuclear neutrophils (PMNs) play critical murine models aim this study was therefore to investigate the putative effects on leukotriene biosynthesis PMN migration through TLR...

ABSTRACT 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 better understanding HHV-6A/B integration mechanism, we made use BRACO-19, compound stabilizes G-quadruplex secondary structures prevents telomere elongation by telomerase complex. First, analyzed folding telomeric sequences binding to BRACO-19 G-quadruplex-specific antibodies surface plasmon resonance. Circular...

Abstract The persistence of SARS-CoV-2 despite the development vaccines and a degree herd immunity is partly due to viral evolution reducing vaccine treatment efficacy. Serial infections wild-type (WT) in Balb/c mice yield mouse-adapted strains with greater infectivity mortality. We investigate if passaging unmodified B.1.351 (Beta) B.1.617.2 (Delta) 20 times K18-ACE2 mice, expressing human ACE2 receptor, BSL-3 laboratory without selective pressures, drives health-relevant lineage-dependent....

Integrons are genetic elements that able to capture genes by a site-specific recombination mechanism. contain gene coding for λ-like integrase carries out interacting with two different target sites; the attI site and palindromic sequence attC (59 base element). Cassette integrations usually involve site, while cassette excisions use attC. Therefore, should bind both sites cleave DNA perform reactions. We have used purified maltose-binding protein fused (MBP-IntI1) native IntI1 gel...

Human herpesvirus 6 (HHV-6) can integrate its genome into the telomeres of host chromosomes and is present in germline about 1 % human population. HHV-6 encodes a putative integrase U94 that possesses all molecular functions required for recombination including DNA-binding, ATPase, helicase nuclease activity, was hypothesized by many researchers to facilitate integration ever since discovery integration. However, analysis virus context has been hampered lack reverse-genetic systems efficient...

Human herpesviruses 6A/B (HHV-6A/B) can integrate their viral genomes in the telomeres of human chromosomes. The and cellular factors contributing to HHV-6A/B integration remain largely unknown, mostly due lack efficient reproducible cell culture models study integration. In this study, we characterized efficiencies several lines using two different approaches. First, after a short-term infection (5 h), cells were processed for single-cell cloning analyzed chromosomally integrated...

Coronavirus disease 19 (COVID-19) is the clinical manifestation of severe acute respiratory syndrome 2 (SARS-CoV-2) infection. A hallmark COVID-19 a lung inflammation characterized by an abundant leukocyte infiltrate, elevated levels cytokines/chemokines, lipid mediators (LMI) and microthrombotic events. Animal models are useful for understanding pathophysiological events leading to COVID-19. One such animal model K18-ACE2 transgenic mice. Despite their importance in inflammation, study LMI...

Immediate-early (IE) proteins are the first expressed following viral entry and play a crucial role in initiation of infection. We report cloning characterization full-length IE1 transcript protein (IE1B) from human herpesvirus 6 (HHV-6) variant B. The IE1B consists five exons (3720 nucleotides), three which coding for protein. 1078-amino acid-long is 62% identical 75% similar to 941-amino acid HHV-6 A. can be detected at 4 h post-infection (P.I.), it distributed as small intranuclear...

Prostaglandin E₂(PGE₂) is an arachidonic acid metabolite mainly produced by activated monocytes/macrophages (Mo/Mφ) that display broad immunomodulatory activities. Several viruses capable of infecting Mo/Mφ modulate PGE₂ synthesis in a way favors the infection processes and spread virions. In present work, we studied effect human herpesvirus 6 (HHV-6) on synthesis. Our results indicate HHV-6 induces<i>COX-2</i> gene expression within few hours infection. We...

Human herpesvirus-6A (HHV-6A) and HHV-6B integrate their genomes into the telomeres of human chromosomes, however, mechanisms leading to integration remain unknown. HHV-6A/B encode a protein that has been proposed be involved in termed U94, an ortholog adeno-associated virus type 2 (AAV-2) Rep68 integrase. In this report, we addressed whether purified recombinant maltose-binding (MBP)-U94 fusion proteins possess biological functions compatible with viral integration. We could demonstrate...

Human herpesviruses 6A and 6B (HHV-6A HHV-6B) are human viruses capable of chromosomal integration. Approximately 1% the population carries one copy HHV-6A/B integrated into every cell in their body, referred to as inherited chromosomally herpesvirus 6A/B (iciHHV-6A/B). Whether iciHHV-6A/B is transcriptionally active vivo how it shapes immunological response still unclear. In this study, we screened DNA sequencing (DNA-seq) transcriptome (RNA-seq) data for 650 individuals available through...

Human herpesvirus-6A (HHV-6A) and 6B (HHV-6B) are two closely related betaherpesviruses that associated with various diseases including seizures encephalitis. The HHV-6A/B genomes have been shown to be present in an integrated state the telomeres of latently infected cells. In addition, integration germ cells has resulted individuals harboring this inherited chromosomally (iciHHV-6) every cell their body. Until now, viral transcriptome epigenetic modifications contribute silencing virus...

Abstract Viral infection often trigger an ATM serine/threonine kinase (ATM)-dependent DNA damage response in host cells that suppresses viral replication. Viruses evolved different strategies to counteract this antiviral surveillance system. Here, we report human herpesvirus 6B (HHV-6B) causes genomic instability by suppressing signaling cells. Expression of immediate-early protein 1 (IE1) phenocopies phenotype and blocks homology-directed double-strand break repair. Mechanistically, IE1...

ABSTRACT The site-specific recombinase IntI1 found in class 1 integrons catalyzes the excision and integration of mobile gene cassettes, especially antibiotic resistance with a recombination system. integron integrase belongs to tyrosine (phage integrase) family. members this family, exemplified by lambda integrase, do not share extensive amino acid identities, but three invariant residues are within two regions, designated box I II. Two conserved arginines, one located II, while other...