Abstract:
:Cytomegalovirus (CMV) is a betaherpesvirus that latently infects most adult humans worldwide and is a major cause of morbidity and mortality in immunocompromised hosts. Latent human CMV (HCMV) is believed to reside in precursors of myeloid-lineage leukocytes and monocytes, which give rise to macrophages and dendritic cells (DC). We report here that human monocyte-derived DC (mo-DC) suppress HCMV infection in coculture with infected fibroblast target cells in a manner dependent on the effector-to-target ratio. Intriguingly, optimal activation of mo-DC was achieved under coculture conditions and not by direct infection with HCMV, implying that mo-DC may recognize unique molecular patterns on, or within, infected fibroblasts. We show that HCMV is controlled by secreted factors that act by priming defenses in target cells rather than by direct viral neutralization, but we excluded a role for interferons (IFNs) in this control. The expression of lytic viral genes in infected cells and the progression of infection were significantly slowed, but this effect was reversible, indicating that the control of infection depended on the transient induction of antiviral effector molecules in target cells. Using immediate early or late-phase reporter HCMVs, we show that soluble factors secreted in the cocultures suppress HCMV replication at both stages of the infection and that their antiviral effects are robust and comparable in numerous batches of mo-DC as well as in primary fibroblasts and stromal cells.IMPORTANCE Human cytomegalovirus is a widespread opportunistic pathogen that can cause severe disease and complications in vulnerable individuals. This includes newborn children, HIV AIDS patients, and transplant recipients. Although the majority of healthy humans carry this virus throughout their lives without symptoms, it is not exactly clear which tissues in the body are the main reservoirs of latent virus infection or how the delicate balance between the virus and the immune system is maintained over an individual's lifetime. Here, for the first time, we provide evidence for a novel mechanism of direct virus control by a subset of human innate immune cells called dendritic cells, which are regarded as a major site of virus latency and reactivation. Our findings may have important implications in HCMV disease prevention as well as in development of novel therapeutic approaches.
journal_name
J Viroljournal_title
Journal of virologyauthors
Kasmapour B,Kubsch T,Rand U,Eiz-Vesper B,Messerle M,Vondran FWR,Wiegmann B,Haverich A,Cicin-Sain Ldoi
10.1128/JVI.01138-17subject
Has Abstractpub_date
2017-12-14 00:00:00issue
1eissn
0022-538Xissn
1098-5514pii
JVI.01138-17journal_volume
92pub_type
杂志文章abstract::We recently discovered an expanded family of adeno-associated viruses (AAVs) that show promise as improved gene therapy vectors. In this study we evaluated the potential of vectors based on several of these novel AAVs as vaccine carriers for human immunodeficiency virus type 1 Gag. Studies with mice indicated that vec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01253-07
更新日期:2007-11-01 00:00:00
abstract::Exosomes are small vesicles secreted from cells that participate in intercellular communication events. Accumulating evidence demonstrates that host exosome pathways are hijacked by viruses and that virally modified exosomes contribute to virus spread and immune evasion. In the case of tumor viruses, recent findings s...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.02470-14
更新日期:2015-05-01 00:00:00
abstract::Insertion of a region, including the 18-nucleotide-long intergenic sequence between genes 6 and 7 of mouse hepatitis virus (MHV) genomic RNA, into an MHV defective interfering (DI) RNA leads to transcription of subgenomic DI RNA in helper virus-infected cells (S. Makino, M. Joo, and J. K. Makino, J. Virol. 66:6031-604...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.6.3304-3311.1993
更新日期:1993-06-01 00:00:00
abstract::Vesicular stomatitis virus (VSV) is a prototype nonsegmented, negative-sense virus used to examine viral functions of a broad family of viruses, including human pathogens. Here we demonstrate that S(2) VSV, an isolate with a small plaque phenotype compared to other Indiana strain viruses, has a transcription defect re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00358-12
更新日期:2012-08-01 00:00:00
abstract::Infectious cDNA corresponding to the entire genome of the attenuated Sabin strain of type 1 poliovirus has been inserted into EcoRI site of bacterial plasmid pBR325. Two consecutive PstI fragments (nucleotide positions 1814 to 3421) of the infectious cDNA of the Sabin 1 strain were replaced by the corresponding DNA fr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.3.786-792.1985
更新日期:1985-03-01 00:00:00
abstract::Simian virus 40 tumor (T) antigen, an established viral oncoprotein, causes alterations in cell growth control through interacting with, and altering the function of, cellular proteins. To examine the effects of T antigen on cell growth control, and to identify the cellular proteins with which it may functionally inte...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.2.756-763.1995
更新日期:1995-02-01 00:00:00
abstract::Stress signaling from mitochondria and the endoplasmic reticulum (ER) leads to the induction of the proapoptotic transcription factor CHOP/GADD153. Many viruses use the ER as a site of replication and/or envelopment, and this activity can lead to the activation of ER stress and apoptosis. African swine fever virus (AS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.19.10825-10828.2004
更新日期:2004-10-01 00:00:00
abstract::Rubella virus contains three structural proteins, capsid, E2, and E1. E2 and E1 are type I membrane glycoproteins that form a heterodimer in the endoplasmic reticulum (ER) before they are transported to and retained in the Golgi complex, where virus assembly occurs. The bulk of unassembled E2 and E1 subunits are not t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.10.7670-7680.1997
更新日期:1997-10-01 00:00:00
abstract::Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01089-17
更新日期:2017-09-27 00:00:00
abstract::Despite the long-standing observation that herpes simplex virus (HSV) latency-associated transcript (LAT) promoter deletion viruses show impaired recurrence phenotypes in relevant animal models, the mechanism by which these sequences exert this phenotypic effect is unknown. We constructed and evaluated four mutant HSV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00642-18
更新日期:2018-06-29 00:00:00
abstract::The Friend or Moloney mink cell focus-forming (MCF) virus encodes a recombinant-type envelope glycoprotein, gp70, that is closely related to the membrane glycoprotein, gp55, of Friend spleen focus-forming virus (SFFV). We have shown previously that gp55 has the ability to activate cell growth by binding to the cellula...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.5.2408-2414.1991
更新日期:1991-05-01 00:00:00
abstract::Chimeric human immunodeficiency virus type 1 (HIV-1) molecular clones differing only in the envelope V3 region were constructed. The V3 regions were derived from two HIV-1 isolates with a non-syncytium-inducing, non-T-cell-tropic phenotype and from four HIV-1 isolates with a syncytium-inducing, T-cell-tropic phenotype...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.757-765.1992
更新日期:1992-02-01 00:00:00
abstract::The deoxyribonucleic acid (DNA) of Escherichia coli B is converted by colicin E2 to products soluble in cold trichloroacetic acid; we show that this DNA degradation (hereafter termed solubilization) is subject to inhibition by infection with bacteriophage T4. At least two modes of inhibition may be differentiated on t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.8.3.303-310.1971
更新日期:1971-09-01 00:00:00
abstract::Preferential integration into transcriptionally active regions of genomes has been observed for retroviral vectors based on gamma-retroviruses and lentiviruses. However, differences in the integration site preferences were detected, which might be explained by differences in viral components of the preintegration comp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00373-06
更新日期:2006-08-01 00:00:00
abstract::Hepatitis C virus core protein forms the viral nucleocapsid and plays a critical role in the formation of infectious particles. In this study, we demonstrate that the highly conserved residue G33, located within domain 1 of the core protein, is important for the production of cell culture-infectious virus (HCVcc). Ala...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05452-11
更新日期:2012-01-01 00:00:00
abstract:UNLABELLED:Hepatitis B, which caused by hepatitis B virus (HBV) infection, remains a major health threat worldwide. Hepatic injury and regeneration from chronic inflammation are the main driving factors of liver fibrosis and cirrhosis in chronic hepatitis B. Proinflammatory tumor necrosis factor alpha (TNF-α) has been ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03106-14
更新日期:2015-02-01 00:00:00
abstract::The fusogenic properties of the uncleaved spike (S) protein of murine coronavirus JHMV variant cl-2 were studied by expressing the S protein with a deleted putative cleavage site. The amino acid sequence of the putative cleavage site, Arg-Arg-Ala-Arg-Arg, was replaced by Arg-Thr-Ala-Leu-Glu by in vitro mutagenesis of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.3.1195-1202.1993
更新日期:1993-03-01 00:00:00
abstract::Recombinant vaccinia viruses expressing C-terminally truncated E's that ranged in length from 9 to 99% of the N-terminal sequence were constructed. The overall antigenicity of the E products was analyzed by radioimmunoprecipitation, using dengue virus hyperimmune mouse ascitic fluid (HMAF) or an anti-E peptide serum. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.3.1400-1407.1991
更新日期:1991-03-01 00:00:00
abstract::Mason-Pfizer monkey virus 60-70S RNA has a molecular weight of 8 times 10-6 when analyzed on polyacrylamide gels. Dissociation of 60-70S RNA of Mason-Pfizer monkey virus and murine leukemia virus by heat or formamide (40%) resulted in conversion to identical subunit structures of 2.8 times 10-6 daltons; treatment with...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.2.423-427.1975
更新日期:1975-02-01 00:00:00
abstract::Nonglucosylated T6 phage (T6gtam 16am30, hereafter called T6alpha gt-) were found to have two structural anomalies when compared with wild-type T6. The DNA of T6alpha gt- phage contains single-strand interruptions. These can be seen both during infection, in the pool of replicating DNA, and in DNA extracted from purif...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.4.776-784.1975
更新日期:1975-04-01 00:00:00
abstract::Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00012-13
更新日期:2013-06-01 00:00:00
abstract::The transcription map of the Aedes albopictus densovirus (AalDNV) brevidensovirus was identified by Northern blotting, rapid amplification of cDNA ends (RACE) analysis, and RNase protection assays. AalDNV produced mRNAs of 3,359 (NS1), 3,345 (NS2), and 1,246 (VP) nucleotides. The two overlapping P7/7.4 NS promoters em...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01259-13
更新日期:2013-09-01 00:00:00
abstract::Epstein-Barr virus (EBV) is a ubiquitous human pathogen associated with Burkitt's lymphoma and nasopharyngeal carcinoma. Although the EBV genome harbors more than a hundred genes, a full transcription map with EBV polyadenylation profiles remains unknown. To elucidate the 3' ends of all EBV transcripts genome-wide, we...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01593-18
更新日期:2019-01-04 00:00:00
abstract::The phylogeny of reptilian herpesviruses (HVs) relative to mammalian and avian HVs was investigated by using available gene sequences and by alignment of encoded amino acid sequences and derivation of trees by maximum-likelihood and Bayesian methods. Phylogenetic loci were obtained for green turtle HV (GTHV) primarily...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.2.725-731.2005
更新日期:2005-01-01 00:00:00
abstract::Changes in the envelope glycoprotein ectodomains of a nonpathogenic simian-human immunodeficiency virus (SHIV-89.6) that was serially passaged in vivo have been shown to be responsible for the increased pathogenicity of the resulting virus, SHIV-KB9 (G. B. Karlsson, et al., J. Exp. Med. 188:1159-1171, 1998). The 12 am...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.9.4433-4440.2000
更新日期:2000-05-01 00:00:00
abstract::The buoyant density characteristics of infectious particles of herpes simplex virus types 1 and 2 were studied by centrifugation in sucrose and cesium chloride density gradients with a high resolution and satisfactory infectivity recovery. It was shown that two populations of infectious virions differing in buoyant de...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.2.737-748.1981
更新日期:1981-05-01 00:00:00
abstract::RNA transfer (Northern) blot analysis was used to perform the physical characterization of the transcript expressed in murine sensory nerve ganglia latently infected with herpes simplex virus type 1. Most of this latency-associated transcript (LAT) was isolated in the poly(A)- fraction from ganglia. A smaller RNA spec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.4.1194-1202.1988
更新日期:1988-04-01 00:00:00
abstract::Avian leukosis virus subgroup J (ALV-J), an exogenous avian retrovirus, is thought to have evolved by recombination with the highly identical env gene of the endogenous avian retrovirus EAV-HP. Embryonic expression of EAV-HP env has been suggested to be associated with the induction of immunological tolerance, a featu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.23.11935-11938.2001
更新日期:2001-12-01 00:00:00
abstract::Disulfide bonds reportedly stabilize the capsids of several viruses, including papillomavirus, polyomavirus, and simian virus 40, and have been detected in herpes simplex virus (HSV) capsids. In this study, we show that in mature HSV-1 virions, capsid proteins VP5, VP23, VP19C, UL17, and UL25 participate in covalent c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00214-11
更新日期:2011-09-01 00:00:00
abstract::Infection of quiescent cells by human cytomegalovirus (HCMV) elicits severe cell cycle deregulation, resulting in a G(1)/S arrest, which can be partly attributed to the inactivation of the anaphase-promoting complex (APC). As we previously reported, the premature phosphorylation of its coactivator Cdh1 and/or the diss...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01260-10
更新日期:2010-10-01 00:00:00