2012 Fiscal Year Final Research Report
A bioinformatics approach toward understanding interplay betweenchronic virus infections and human antiviral immune responses
| Project/Area Number |
23659232
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | Kumamoto University |
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Principal Investigator |
UENO Takamasa 熊本大学, エイズ学研究センター, 准教授 (10322314)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 感染防御 / ワクチン |
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| Research Abstract |
HIV -1 Nef is required for efficient viral replication and pathogenesis. However , the extent to which Nef ’ s functions are maintained in natural sequences duringchronic infection, and their clinical relevance, remains incompletely characterized. Relativeto a control Nef from HIV -1 strain SF2, HLA class I and CD4 down-regulation activities of46 plasma RNA Nef sequences derived from unique chronic infected individuals weregenerally high and displayed narrow dynamic ranges, whereas Nef-mediated virioninfectivity , PBMC replication and CD74 up-regulation exhibited broader dynamic ranges.80% of patient-derived Nefs were active for at least three functions examined. Functionalco-dependencies were identified, including positive correlations between CD4down-regulation and virion infectivity , replication, and CD74 up-regulation, and betweenCD74 up-regulation and PBMC replication. Nef-mediated virion infectivity inverselycorrelated with patient CD4+ T -cell count. Strong functional co-dependencies and thepolyfunctional nature of patient-derived Nef sequences suggest a phenotypic requirementto maintain multiple Nef functions during chronic infection
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[Journal Article] Attenuation of multiple Neffunctions in HIV-1 elite controllers2013
Author(s)
Philip Mwimanzi, Tristan J Markle,Eric Martin, Yoko Ogata, Xiaomei TKuang, Michiyo Tokunaga, MacdonaldMahiti, Florencia Pereyra, ToshiyukiMiura, Bruce D Walker, Zabrina L Brumme,Mark A Brockman and *Takamasa Ueno
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Journal Title
Retrovirology
Volume: 10
Pages: 1
DOI
Peer Reviewed
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