Abstract:
:Chronic infections with viruses such as hepatitis B virus, hepatitis C virus, and HIV constitute a major global public health problem. Studies of chronic viral infections in humans and mice show that persistent antigenic stimulation induces dysregulation of T cell responses; virus-specific T cells either undergo clonal deletion or lose their ability to display the full spectrum of effector functions, a condition termed functional exhaustion. The ability to generate and retain sufficient numbers of functionally competent T cells, therefore, becomes vitally important in controlling chronic viral infections. Our understanding of the mechanisms governing T cell homeostasis during chronic viral infections, however, is poor. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway controls cell fate decisions in many cell types by modulating the activity of downstream effectors, including the FOXO family of transcription factors. We have observed dynamic, in vivo alterations in the phosphorylation levels of three key proteins (Akt, FOXO1/FOXO3 [FOXO1/3], and mammalian target of rapamycin [mTOR]) involved in this signaling cascade and have identified the transcription factor FOXO3 as a negative regulator of the magnitude and effector function of CD8 T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. We report that ablation of FOXO3 in T cells reduced apoptosis, increased the abundance of polyfunctional virus-specific CD8 T cells, and improved viral control. Thus, FOXO3 is a promising candidate target for immunotherapies of chronic viral infection.
journal_name
J Viroljournal_title
Journal of virologyauthors
Sullivan JA,Kim EH,Plisch EH,Suresh Mdoi
10.1128/JVI.00942-12subject
Has Abstractpub_date
2012-09-01 00:00:00pages
9025-34issue
17eissn
0022-538Xissn
1098-5514pii
JVI.00942-12journal_volume
86pub_type
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doi:10.1128/JVI.12.5.995-1005.1973
更新日期:1973-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:1986-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1989-10-01 00:00:00
abstract::Mutations at amino acids 143, 148, and 155 in HIV-1 integrase (IN) define primary resistance pathways in subjects failing raltegravir (RAL)-containing treatments. Although each pathway appears to be genetically distinct, shifts in the predominant resistant virus population have been reported under continued drug press...
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pub_type: 杂志文章
doi:10.1128/JVI.06618-11
更新日期:2012-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.68.11.7178-7187.1994
更新日期:1994-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1999-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-06-01 00:00:00
abstract::The membrane fusion events which initiate human immunodeficiency virus type 1 (HIV-1) infection and promote cytopathic syncytium formation in infected cells commence with the binding of the HIV envelope glycoprotein (Env) to CD4 and an appropriate coreceptor. Here, we show that HIV Env-coreceptor interactions activate...
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pub_type: 杂志文章
doi:10.1128/JVI.78.13.7138-7147.2004
更新日期:2004-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.01095-14
更新日期:2014-11-01 00:00:00
abstract:UNLABELLED:The HIV-1 virion infectivity factor (Vif) targets the cellular cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) for degradation via the host ubiquitin-proteasome pathway. Vif recruits a cellular E3 ubiquitin ligase to polyubiquitinate A3G/F. The activity of Vif critically depends on the cellular core bi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03824-13
更新日期:2014-03-01 00:00:00
abstract::Wild-type clones of reovirus serotypes 1 (Lang), 2 (Jones), and 3 (Dearing) were serially passaged in L cells at a high multiplicity of infection, and the virus population was examined at passage levels 2, 5, and 11 for the presence of temperature-sensitive (ts) mutants. By passage 11 all three serotypes contained ts ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.34.1.285-287.1980
更新日期:1980-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00266-07
更新日期:2007-08-01 00:00:00
abstract::Coinfection with HIV-1 and Kaposi's sarcoma-associated herpesvirus (KSHV) often leads to AIDS-related malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). The interaction between HIV and KSHV plays a pivotal role in the progression of these malignancies. We have previously demonstrated th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00580-18
更新日期:2018-08-29 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.3.585-598.1975
更新日期:1975-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2009-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.1.46-59.1981
更新日期:1981-07-01 00:00:00
abstract::Previous analysis of hepatitis B virus (HBV) indicated base pairing between two cis-acting sequences, the 5' half of the upper stem of epsilon and phi, contributes to the synthesis of minus-strand DNA. Our goal was to identify other cis-acting sequences on the pregenomic RNA (pgRNA) involved in the synthesis of minus-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01414-07
更新日期:2007-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.11.5411-5421.2002
更新日期:2002-06-01 00:00:00
abstract:UNLABELLED:The risk of transmission of transmissible spongiform encephalopathies (TSE) between different species has been notoriously unpredictable because the mechanisms of transmission are not fully understood. A transmission barrier between species often prevents infection of a new host with a TSE agent. Nonetheless...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02296-14
更新日期:2015-05-01 00:00:00
abstract::This study identifies memory cytotoxic T lymphocyte (CTL) epitopes to respiratory syncytial virus (RSV) in healthy South African adults and demonstrates the conservation of those epitopes in circulating field strains of RSV in South Africa. Thirty-seven healthy adults from a population with diverse HLA backgrounds wer...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.13.7319-7329.2003
更新日期:2003-07-01 00:00:00
abstract::To combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. Here, we exploit a biosafety level 2 (BSL-2) chimeric Sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01749-14
更新日期:2014-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.5.2646-2654.1993
更新日期:1993-05-01 00:00:00
abstract::The St-1 genome is about 6,050 base pairs in size, approximately 10% larger than phiX174 (5,375 base pairs). The DNA fragments obtained by HincII, HaeIII, and EcoRI digestion were ordered and aligned into a colinear map, and the single BglI cleavage site was located. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.27.3.738-744.1978
更新日期:1978-09-01 00:00:00
abstract::Harvard Medical School convened a meeting of biomedical and clinical experts on 5 March 2015 on the topic of "Rethinking the Response to Emerging Microbes: Vaccines and Therapeutics in the Ebola Era," with the goals of discussing the lessons from the recent Ebola outbreak and using those lessons as a case study to aid...
journal_title:Journal of virology
pub_type: 共识发展会议,杂志文章
doi:10.1128/JVI.01251-15
更新日期:2015-08-01 00:00:00