Abstract:
:Human immunodeficiency virus (HIV) infection is associated with immune activation, CD4⁺-T-cell loss, and a progressive decline of immune functions. Antiretroviral therapy (ART) only partially reverses HIV-associated immune dysfunction, suggesting that approaches that target immune activation and improve virus-specific immune responses may be needed. We performed a preclinical study in rhesus macaques infected with the pathogenic simian immunodeficiency virus SIV(mac251) and treated with ART. We tested whether vaccination administered together with cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) blockade and treatment with the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan (D-1mT), decreased immune activation and improved vaccine efficacy. The treatment did not augment vaccine immunogenicity; rather, it dramatically increased ART-related toxicity, causing all treated animals to succumb to acute pancreatitis and hyperglycemic coma. The onset of fulminant diabetes was associated with severe lymphocyte infiltration of the pancreas and complete loss of the islets of Langerhans. Thus, caution should be used when considering approaches aimed at targeting immune activation during ART.
journal_name
J Viroljournal_title
Journal of virologyauthors
Vaccari M,Boasso A,Fenizia C,Fuchs D,Hryniewicz A,Morgan T,Weiss D,Doster MN,Heraud JM,Shearer GM,Franchini Gdoi
10.1128/JVI.05609-11subject
Has Abstractpub_date
2012-01-01 00:00:00pages
108-13issue
1eissn
0022-538Xissn
1098-5514pii
JVI.05609-11journal_volume
86pub_type
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journal_title:Journal of virology
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/JVI.16.6.1669-1677.1975
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.3.492-500.1973
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pub_type: 杂志文章
doi:10.1128/jvi.76.7.3158-3167.2002
更新日期:2002-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.19.3.1080-1089.1976
更新日期:1976-09-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1969-11-01 00:00:00
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pub_type: 杂志文章,评审
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abstract::The emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants are usually replaced by drug-sensitive ones when the selective pressure of the drugs is removed, as the former have reduced fitness in a drug-free environm...
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pub_type: 杂志文章
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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
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1983-03-01 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:2002-10-01 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:1992-03-01 00:00:00