Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • JSTOR Archival Journals  (4)
Type of Medium
Language
Year
  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 06 August 2013, Vol.110(32), pp.13126-31
    Description: Human CMV (hCMV) establishes lifelong infections in most of us, causing developmental defects in human embryos and life-threatening disease in immunocompromised individuals. During productive infection, the viral 〉230,000-bp dsDNA genome is expressed widely and in a temporal cascade. The hCMV genome does not carry histones when encapsidated but has been proposed to form nucleosomes after release into the host cell nucleus. Here, we present hCMV genome-wide nucleosome occupancy and nascent transcript maps during infection of permissive human primary cells. We show that nucleosomes occupy nuclear viral DNA in a nonrandom and highly predictable fashion. At early times of infection, nucleosomes associate with the hCMV genome largely according to their intrinsic DNA sequence preferences, indicating that initial nucleosome formation is genetically encoded in the virus. However, as infection proceeds to the late phase, nucleosomes redistribute extensively to establish patterns mostly determined by nongenetic factors. We propose that these factors include key regulators of viral gene expression encoded at the hCMV major immediate-early (IE) locus. Indeed, mutant virus genomes deficient for IE1 expression exhibit globally increased nucleosome loads and reduced nucleosome dynamics compared with WT genomes. The temporal nucleosome occupancy differences between IE1-deficient and WT viruses correlate inversely with changes in the pattern of viral nascent and total transcript accumulation. These results provide a framework of spatial and temporal nucleosome organization across the genome of a major human pathogen and suggest that an hCMV major IE protein governs overall viral chromatin structure and function.
    Keywords: Chip-Chip ; Epigenetic Regulation ; Functional Genomics ; Herpesvirus ; Chromatin -- Genetics ; Cytomegalovirus -- Genetics ; Genome, Viral -- Genetics ; Immediate-Early Proteins -- Genetics ; Nucleosomes -- Genetics
    ISSN: 00278424
    E-ISSN: 1091-6490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 07 March 2006, Vol.103(10), pp.3840-5
    Description: Type I IFNs are crucial components of the innate immune response to viral attack. They are rapidly synthesized and secreted after infection with human cytomegalovirus (CMV) and trigger a signal transduction pathway that involves successive activation and nuclear translocation of signal transducer and activator of transcription 1 (STAT1) and STAT2. The activated STATs, together with the IFN regulatory factor 9 protein, form a trimeric transcription complex (IFN-stimulated gene factor 3) that stimulates expression of numerous IFN-responsive genes, many of which exhibit antiviral activity. Here we demonstrate that the viral 72-kDa IE1 protein (IE1-72kDa) confers partial resistance to the antiviral activity of type I IFNs upon CMV. Accordingly, IFN-responsive transcripts accumulate to substantially increased levels after infection with an IE1-deficient mutant as compared with wild-type virus, and ectopic expression of the viral protein in stably transfected cells is sufficient to block their induction. We further show that IE1-72kDa forms a physical complex with STAT1 and STAT2 in nuclei of infected cells and in vitro and prevents association of STAT1, STAT2, and IFN regulatory factor 9 with promoters of IFN-responsive genes in vivo. Our results indicate that the viral protein blocks an intranuclear step after nuclear translocation and before DNA binding of IFN-stimulated gene factor 3, presumably by interfering with the integrity and/or correct subnuclear localization of the protein complex. This study identifies the CMV IE1-72kDa protein as a viral antagonist of the cellular innate immune response, inhibiting IFN-dependent STAT signaling by means of an unprecedented molecular mechanism.
    Keywords: Cytomegalovirus -- Immunology ; Interferon Type I -- Metabolism ; Stat1 Transcription Factor -- Metabolism ; Stat2 Transcription Factor -- Metabolism
    ISSN: 0027-8424
    E-ISSN: 10916490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 07 December 2004, Vol.101(49), pp.17234-9
    Description: The human cytomegalovirus 72-kDa immediate-early (IE)1 and 86-kDa IE2 proteins are expressed at the start of infection, and they are believed to exert much of their function through promiscuous transcriptional activation of viral and cellular gene expression. Here, we show that the impaired growth of an IE1-deficient mutant virus in human fibroblasts is efficiently rescued by histone deacetylase (HDAC) inhibitors of three distinct chemical classes. In the absence of IE1 expression, the viral major IE and UL44 early promoters exhibited decreased de novo acetylation of histone H4 during the early phase of infection, and the hypoacetylation correlated with reduced transcription and accumulation of the respective gene products. Consistent with these findings, IE1 interacts specifically with HDAC3 within infected cells. We also demonstrate an interaction between IE2 and HDAC3. We propose that the ability to modify chromatin is fundamental to transcriptional activation by IE1 and, likely, IE2 as well.
    Keywords: Histone Deacetylase Inhibitors ; Virus Replication ; Immediate-Early Proteins -- Physiology ; Viral Proteins -- Physiology
    ISSN: 0027-8424
    E-ISSN: 10916490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 01 June 2008, Vol.46(11), pp.1677-82
    Description: Antibiotic resistance among microbes urgently necessitates the development of novel antimicrobial agents. Since ancient times, honey has been used successfully for treatment of infected wounds, because of its antibacterial activity. However, large variations in the in vitro antibacterial activity of various honeys have been reported and hamper its acceptance in modern medicine. We assessed the in vitro bactericidal activity of Revamil (Bfactory), a medical-grade honey produced under controlled conditions, and assessed its efficacy for reduction of forearm skin colonization in healthy volunteers in a within-subject-controlled trial. With Bacillus subtilis as a test strain, we demonstrated that the variation in bactericidal activity of 11 batches of medical-grade honey was 〈2-fold. Antibiotic-susceptible and -resistant isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, and Klebsiella oxytoca were killed within 24 h by 10%-40% (vol/vol) honey. After 2 days of application of honey, the extent of forearm skin colonization in healthy volunteers was reduced 100-fold (P 〈 .001), and the numbers of positive skin cultures were reduced by 76% (P 〈 .001). Revamil is a promising topical antimicrobial agent for prevention or treatment of infections, including those caused by multidrug-resistant bacteria.
    Keywords: Honey ; Anti-Bacterial Agents -- Therapeutic Use ; Bacteria -- Drug Effects ; Skin Diseases, Bacterial -- Drug Therapy
    ISSN: 10584838
    E-ISSN: 1537-6591
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages