Preemptive CD8 T-cell immunotherapy of acute cytomegalovirus infection prevents lethal disease, limits the burden of latent viral genomes, and reduces the risk of virus recurrence.

Abstract:

:In the immunocompetent host, primary cytomegalovirus (CMV) infection is resolved by the immune response without causing overt disease. The viral genome, however, is not cleared but is maintained in a latent state that entails a risk of virus recurrence and consequent organ disease. By using murine CMV as a model, we have shown previously that multiple organs harbor latent CMV and that reactivation occurs with an incidence that is determined by the viral DNA load in the respective organ (M. J. Reddehase, M. Balthesen, M. Rapp, S. Jonjic, I. Pavic, and U. H. Koszinowski. J. Exp. Med. 179:185-193, 1994). This predicts that a therapeutic intervention capable of limiting the load of latent viral genome should also reduce the risk of virus recurrence. Here we demonstrate the benefits and the limits of a preemptive CD8 T-cell immunotherapy of CMV infection in the immunocompromised bone marrow transplantation recipient. Antiviral CD8 T cells prevented CMV disease and accelerated the resolution of productive infection. The therapy also resulted in a lower load of latent CMV DNA in organs and consequently reduced the incidence of recurrence. The data thus provide a further supporting argument for clinical trials of preemptive cytoimmunotherapy of human CMV disease with CD8 T cells. However, CD8 T cells failed to clear the viral DNA. The therapy-susceptible portion of the DNA load differed between organs and was highest in the lungs. The existence of an invariant, therapy-resistant load suggests a role for immune system evasion mechanisms in the establishment of CMV latency.

journal_name

J Virol

journal_title

Journal of virology

authors

Steffens HP,Kurz S,Holtappels R,Reddehase MJ

doi

10.1128/JVI.72.3.1797-1804.1998

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

1797-804

issue

3

eissn

0022-538X

issn

1098-5514

journal_volume

72

pub_type

杂志文章
  • The myxoma virus m-t5 ankyrin repeat host range protein is a novel adaptor that coordinately links the cellular signaling pathways mediated by Akt and Skp1 in virus-infected cells.

    abstract::Most poxviruses express multiple proteins containing ankyrin (ANK) repeats accounting for a large superfamily of related but unique determinants of poxviral tropism. Recently, select members of this novel family of poxvirus proteins have drawn considerable attention for their potential roles in modulating intracellula...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00963-09

    authors: Werden SJ,Lanchbury J,Shattuck D,Neff C,Dufford M,McFadden G

    更新日期:2009-12-01 00:00:00

  • Functional analysis of the murine sarcoma virus RNA packaging sequence.

    abstract::We investigated the features of the Moloney murine sarcoma virus leader sequence necessary for RNA packaging function by using a deletion analysis approach. We found that sequences that extend beyond those characterized genetically in previous reports are important for optimal packaging efficiency. A fragment covering...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.76.9.4643-4648.2002

    authors: Izmailova E,Aldovini A

    更新日期:2002-05-01 00:00:00

  • Multivariate analysis of human immunodeficiency virus type 1 neutralization data.

    abstract::We report on the use of spectral map analysis of the inter- and intraclade neutralization data of 14 sera of human immunodeficiency virus type 1 (HIV-1)-infected individuals and 16 primary isolates, representing genetic clades A to H in group M and group O. This multivariate analysis has been used previously to study ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.9.6235-6243.1996

    authors: Nyambi PN,Nkengasong J,Lewi P,Andries K,Janssens W,Fransen K,Heyndrickx L,Piot P,van der Groen G

    更新日期:1996-09-01 00:00:00

  • Functional characterization of thermolabile DNA-binding proteins that affect adenovirus DNA replication.

    abstract::The human adenovirus type 2 (Ad2) mutant Ad2ts111 has previously been shown to contain two mutations which result in a complex phenotype. Ad2ts111 contains a single base change in the early region 1B (E1B) 19,000-molecular-weight (19K) coding region which yields a cyt deg phenotype and another defect which maps to the...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.57.3.883-892.1986

    authors: Prelich G,Stillman BW

    更新日期:1986-03-01 00:00:00

  • Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus.

    abstract::Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01926-07

    authors: Hon CC,Lam TY,Shi ZL,Drummond AJ,Yip CW,Zeng F,Lam PY,Leung FC

    更新日期:2008-02-01 00:00:00

  • Rationally Designed Immunogens Targeting HIV-1 gp120 V1V2 Induce Distinct Conformation-Specific Antibody Responses in Rabbits.

    abstract::The V1V2 region of HIV-1 gp120 harbors a major vulnerable site targeted by a group of broadly neutralizing monoclonal antibodies (MAbs) such as PG9 through strand-strand recognition. However, this epitope region is structurally polymorphic as it can also form a helical conformation recognized by RV144 vaccine-induced ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01409-16

    authors: Jiang X,Totrov M,Li W,Sampson JM,Williams C,Lu H,Wu X,Lu S,Wang S,Zolla-Pazner S,Kong XP

    更新日期:2016-11-28 00:00:00

  • Monoclonal antibodies against the minimal DNA-binding domain in the carboxyl-terminal region of human immunodeficiency virus type 1 integrase.

    abstract::Integrase of human immunodeficiency virus type 1 (HIVIN) consists of 288 amino acids, and its minimum DNA-binding domain (MDBD) (amino acids [aa] 220 to 270) is required for the integration reaction. We produced and characterized four murine monoclonal antibodies (MAbs) to the MDBD of HIVIN (strain LAI). Immunoblot an...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.5.4475-4480.1999

    authors: Ishikawa T,Okui N,Kobayashi N,Sakuma R,Kitamura T,Kitamura Y

    更新日期:1999-05-01 00:00:00

  • Conformational changes in the VP1-unique region of native human parvovirus B19 lead to exposure of internal sequences that play a role in virus neutralization and infectivity.

    abstract::The unique region of the capsid protein VP1 (VP1u) of human parvovirus B19 (B19) elicits a dominant immune response and has a phospholipase A(2) (PLA(2)) activity, which is necessary for the infection. In contrast to the rest of the parvoviruses, the VP1u of B19 is thought to occupy an external position in the virion,...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01435-06

    authors: Ros C,Gerber M,Kempf C

    更新日期:2006-12-01 00:00:00

  • Icam-1 participates in the entry of west nile virus into the central nervous system.

    abstract::Determining how West Nile virus crosses the blood-brain barrier is critical to understanding the pathogenesis of encephalitis. Here, we show that ICAM-1(-/-) mice are more resistant than control animals to lethal West Nile encephalitis. ICAM-1(-/-) mice have a lower viral load, reduced leukocyte infiltration, and dimi...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02621-07

    authors: Dai J,Wang P,Bai F,Town T,Fikrig E

    更新日期:2008-04-01 00:00:00

  • Localization of sequences responsible for trans-activation of the equine infectious anemia virus long terminal repeat.

    abstract::We used the Escherichia coli chloramphenicol acetyltransferase gene (cat) to study sequences that influence expression of the equine infectious anemia virus (EIAV) genome. The EIAV long terminal repeat (LTR) directed CAT activity in a canine cell line, but at levels much lower than those achieved with other eucaryotic...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.62.1.120-126.1988

    authors: Sherman L,Gazit A,Yaniv A,Kawakami T,Dahlberg JE,Tronick SR

    更新日期:1988-01-01 00:00:00

  • Adult AIDS-like disease in a novel inducible human immunodeficiency virus type 1 Nef transgenic mouse model: CD4+ T-cell activation is Nef dependent and can occur in the absence of lymphophenia.

    abstract::CD4C/HIV(nef) transgenic (Tg) mice express Nef in CD4+ T cells and in the cells of the macrophage/monocyte/dendritic lineage, and they develop an AIDS-like disease similar to human AIDS. In these mice, Nef is constitutively expressed throughout life. To rule out the contribution of any developmental defects caused by ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01466-09

    authors: Rahim MM,Chrobak P,Hu C,Hanna Z,Jolicoeur P

    更新日期:2009-11-01 00:00:00

  • Mechanism of release of active alpha subunit from dimeric alpha beta avian myeloblastosis virus DNA polymerase.

    abstract::Storage of the dimeric (alphabeta) form of avian myeloblastosis virus (AMV) DNA polymerase in glycerol resulted in the release of the smaller alpha subunit, as detected by glycerol gradient sedimentation. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of enzyme stored in glycerol showed the conc...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.18.3.904-910.1976

    authors: Papas TS,Marciani DJ,Samuel K,Chirikjian JG

    更新日期:1976-06-01 00:00:00

  • Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells.

    abstract::The 55-kDa E1B protein of adenovirus, which binds to and inactivates the tumor suppressor protein p53, is not expressed in the adenoviral mutant termed ONYX-015 (i.e., dl1520). It was reported that the mutant virus due to a deletion in E1B is able to replicate only in cells deficient for wild-type p53. Accordingly, dl...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.72.12.9470-9478.1998

    authors: Rothmann T,Hengstermann A,Whitaker NJ,Scheffner M,zur Hausen H

    更新日期:1998-12-01 00:00:00

  • Replication of hepatitis delta virus RNA: effect of mutations of the autocatalytic cleavage sites.

    abstract::Hepatitis delta virus (HDV) contains a circular RNA genome of 1.7 kb. HDV RNA replication is thought to proceed via a rolling-circle mechanism that is dependent on autocatalytic cleavage and ligation reactions. However, it has never been established that these ribozyme activities are indeed involved in HDV RNA replica...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.67.4.2228-2234.1993

    authors: Macnaughton TB,Wang YJ,Lai MM

    更新日期:1993-04-01 00:00:00

  • Recombinant nipah virus vaccines protect pigs against challenge.

    abstract::Nipah virus (NiV), of the family Paramyxoviridae, was isolated in 1999 in Malaysia from a human fatality in an outbreak of severe human encephalitis, when human infections were linked to transmission of the virus from pigs. Consequently, a swine vaccine able to abolish virus shedding is of veterinary and human health ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00263-06

    authors: Weingartl HM,Berhane Y,Caswell JL,Loosmore S,Audonnet JC,Roth JA,Czub M

    更新日期:2006-08-01 00:00:00

  • Design and Structure of an Engineered Disulfide-Stabilized Influenza Virus Hemagglutinin Trimer.

    abstract::We engineered a disulfide-stabilized influenza virus hemagglutinin (HA) trimer, termed HA3-SS, by introducing cysteine residues into the HA stem to covalently bridge the three protomers. HA3-SS has increased thermostability compared to wild-type HA, and binding of head- and stem-targeted antibodies (Abs) is preserved;...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00808-15

    authors: Lee PS,Zhu X,Yu W,Wilson IA

    更新日期:2015-07-01 00:00:00

  • Degradation of tobacco mosaic virus movement protein by the 26S proteasome.

    abstract::Cell-to-cell spread of tobacco mosaic virus is facilitated by the virus-encoded 30-kDa movement protein (MP). This process involves interaction of viral proteins with host components, including the cytoskeleton and the endoplasmic reticulum (ER). During virus infection, high-molecular-weight forms of MP were detected ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.7.3330-3337.2000

    authors: Reichel C,Beachy RN

    更新日期:2000-04-01 00:00:00

  • Suppression of Leishmania RNA virus replication by capsid protein overexpression.

    abstract::Some strains of the protozoan parasite genus Leishmania are persistently infected with single-segmented double-stranded RNA viruses, which are termed LRV. The function of these cytoplasmic viruses is unknown. In order to address the question of whether LRV affects the parasite's phenotype, pairs of isogenic LRV(+)-LRV...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.69.7.4122-4126.1995

    authors: Widmer G

    更新日期:1995-07-01 00:00:00

  • Oligomer formation of the gB glycoprotein of herpes simplex virus type 1.

    abstract::Oligomer formation of the gB glycoprotein of herpes simplex virus type 1 was studied by sedimentation analysis of radioactively labeled infected cell and virion lysates. Fractions from sucrose gradients were precipitated with a pool of gB-specific monoclonal antibodies and analyzed by sodium dodecyl sulfate-polyacryla...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.8.4275-4283.1991

    authors: Highlander SL,Goins WF,Person S,Holland TC,Levine M,Glorioso JC

    更新日期:1991-08-01 00:00:00

  • Genetic Analyses of Contributions of Viral Interleukin-6 Interactions and Signaling to Human Herpesvirus 8 Productive Replication.

    abstract::Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) is a cytokine that is poorly secreted and localized largely to the endoplasmic reticulum (ER). It has been implicated, along with other HHV-8 proinflammatory and/or angiogenic viral proteins, in HHV-8-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00909-20

    authors: Li Q,Xiang Q,Chen D,Nicholas J

    更新日期:2020-09-15 00:00:00

  • Dynamics and modulation of human immunodeficiency virus type 1 transcripts in vitro and in vivo.

    abstract::The dynamics of human immunodeficiency virus type 1 (HIV-1) transcription was analyzed in vitro and in vivo by using a specific molecular approach which allows accurate quantitation of the different classes of viral mRNAs. Unspliced (US) and multiply spliced (MS) HIV-1 transcripts were assayed by competitive reverse t...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.11.7603-7613.1996

    authors: Bagnarelli P,Valenza A,Menzo S,Sampaolesi R,Varaldo PE,Butini L,Montroni M,Perno CF,Aquaro S,Mathez D,Leibowitch J,Balotta C,Clementi M

    更新日期:1996-11-01 00:00:00

  • Herpes simplex virus 1 has multiple mechanisms for blocking virus-induced interferon production.

    abstract::In response to viral infection, host cells elicit a number of responses, including the expression of alpha/beta interferon (IFN-alpha/beta). In these cells, IFN regulatory factor-3 (IRF-3) undergoes a sequence of posttranslational modifications that allow it to act as a potent transcriptional coactivator of specific I...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.16.8411-8420.2004

    authors: Melroe GT,DeLuca NA,Knipe DM

    更新日期:2004-08-01 00:00:00

  • Characterization of a bacteriophage related to R-type pyocins.

    abstract::A bacteriophage with a contractile tail which shows very similar features to R-type pyocins was isolated and characterized. This phage, named PS17,was purified by DEAE-cellulose chromatography and CsCl density gradient centrifugation. It was a DNA-containing phage, and the density of the purified particles in CsCl was...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.32.3.951-957.1979

    authors: Kageyama M,Shinomiya T,Aihara Y,Kobayashi M

    更新日期:1979-12-01 00:00:00

  • Stimulus duration and response time independently influence the kinetics of lytic cycle reactivation of Epstein-Barr virus.

    abstract::Epstein-Barr virus (EBV) can be reactivated from latency into the lytic cycle by many stimuli believed to operate by different mechanisms. Cell lines containing EBV differ in their responses to inducing stimuli, yet all stimuli require de novo protein synthesis (44). A crucial step preliminary to identifying these pro...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01172-09

    authors: Countryman J,Gradoville L,Bhaduri-McIntosh S,Ye J,Heston L,Himmelfarb S,Shedd D,Miller G

    更新日期:2009-10-01 00:00:00

  • Site-Specific Recombination by SSV2 Integrase: Substrate Requirement and Domain Functions.

    abstract:UNLABELLED:SSV-type integrases, encoded by fuselloviruses which infect the hyperthermophilic archaea of the Sulfolobales, are archaeal members of the tyrosine recombinase family. These integrases catalyze viral integration into and excision from a specific site on the host genome. In the present study, we have establis...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01637-15

    authors: Zhan Z,Zhou J,Huang L

    更新日期:2015-11-01 00:00:00

  • Cytomegalovirus inhibits the engraftment of donor bone marrow cells by downregulation of hemopoietin gene expression in recipient stroma.

    abstract::Cytomegalovirus (CMV) disease after bone marrow (BM) transplantation is often associated with BM graft failure. There are two possible reasons for such a correlation. First, a poor hematopoietic reconstitution of unrelated etiology could promote the progression of CMV infection by the lack of immune control. Alternati...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.72.6.5006-5015.1998

    authors: Steffens HP,Podlech J,Kurz S,Angele P,Dreis D,Reddehase MJ

    更新日期:1998-06-01 00:00:00

  • The Lymantria dispar nucleopolyhedrovirus enhancins are components of occlusion-derived virus.

    abstract::Enhancins are metalloproteinases, first identified in granuloviruses, that can enhance nucleopolyhedrovirus (NPV) potency. We had previously identified two enhancin genes (E1 and E2) in the Lymantria dispar multinucleocapsid NPV (LdMNPV) and showed that both were functional. For this study, we have extended our analys...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.16.10578-10588.2005

    authors: Slavicek JM,Popham HJ

    更新日期:2005-08-01 00:00:00

  • Modulation by gamma interferon of antiviral cell-mediated immune responses in vivo.

    abstract::Mice were infected with lymphocytic choriomeningitis virus and injected once 24 h later with a monoclonal antibody directed against gamma interferon. In comparison with controls, the increase of numbers of CD8+ T cells and the generation of virus-specific cytotoxic T lymphocytes in spleens and virus clearance from org...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.3.1521-1526.1996

    authors: Utermöhlen O,Dangel A,Tárnok A,Lehmann-Grube F

    更新日期:1996-03-01 00:00:00

  • Sequence, function, and regulation of the Vmw65 gene of herpes simplex virus type 2.

    abstract::We determined the sequence of the gene for the virion transactivator protein Vmw65 of herpes simplex virus type 2 (HSV-2), strain 333. An analysis of the coding sequence revealed an overall high degree of primary sequence conservation (86%) relative to the HSV-1 protein, although the carboxy-terminal region which enco...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.12.6705-6713.1991

    authors: Greaves RF,O'Hare P

    更新日期:1991-12-01 00:00:00

  • Comparison of transformation and T antigen induction in human cell lines.

    abstract::Skin fibroblast cultures were established from eight individuals. These cell cultures, together with WI-38 cells, were examined for susceptibility to transformation by SV40 virus. Four transformation-susceptible cell lines (TS), established from patients with Down's syndrome, were found to be three to four times more ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.5.3.293-298.1970

    authors: Potter CW,Potter AM,Oxford JS

    更新日期:1970-03-01 00:00:00