Biomedical subjects

Sang Kyung Lee

Publications and source records attributed to Sang Kyung Lee.

3 recordsLinked to original sources

PubMed2006

Interfering antiviral immunity: application, subversion, hope?

RNA interference (RNAi), initially recognized as a natural antiviral mechanism in plants, has rapidly emerged as an invaluable tool to suppress gene expression in a sequence-specific manner in all organisms, including mammals. Its potential to inhibit the replication of a variety of viruses has been demonstrated in vitro and in vivo in mouse and monkey models. These results have generated profound interest in the use of this technology as a potential treatment strategy for viral infections for which vaccines and drugs are unavailable or inadequate. In this review, we discuss the progress made within the past 2-3 years towards harnessing the potential of RNAi for clinical application in viral infections and the hurdles that have yet to be overcome.

Animals↗

PubMed2006

A single siRNA suppresses fatal encephalitis induced by two different flaviviruses.

BACKGROUND: Japanese encephalitis virus (JEV) and West Nile virus (WNV) are neurotropic flaviviruses that can cause acute encephalitis with a high fatality rate. Currently there is no effective treatment for these infections. METHODS AND FINDINGS: We tested RNA interference (RNAi)-based intervention to suppress lethal JE and WN encephalitis in mice. To induce RNAi, we used either lentivirally expressed short hairpin RNA (shRNA) or synthetic short interfering RNA (siRNA). As target, we selected the cd loop-coding sequence in domain II of the viral Envelope protein, which is highly conserved among all flaviviruses because of its essential role in membrane fusion. Using as a target a species-specific sequence in the cd loop that is conserved only among the different strains of either JEV or WNV, we could achieve specific protection against the corresponding virus. However, by targeting a cross-species conserved sequence within the cd loop, we were able to protect mice against encephalitis induced by both viruses. A single intracranial administration of lentivirally delivered shRNA or lipid-complexed siRNA before viral challenge or siRNA treatment after viral challenge was sufficient for protection against lethal encephalitis. CONCLUSIONS: RNAi-based intervention affords near complete protection from both JEV- and WNV- induced encephalitis in mice. Our results show, to our knowledge for the first time, that siRNA can be used as a broad-spectrum antiviral agent for treating encephalitis caused by multiple related viruses.

Animals↗

PubMed2002

The functional CD8 T cell response to HIV becomes type-specific in progressive disease.

High levels of HIV-specific CD8 T cells are demonstrable throughout HIV disease using laboratory assays that measure responses to consensus epitopes. In acute infection, the dynamics of the antiviral CD8 T cell response correlate well with the decline in viremia. However in chronic infection, although responses are detected against a broader spectrum of epitopes, virus-specific CD8 T cells are apparently unable to control viral replication. To investigate whether CD8 T cells responding to consensus epitopes may have lost their in vivo relevance in the chronic phase because of viral evolution driven by immune pressure, we compared the CD8 T cell response to CD4 T cell targets infected with either lab-adapted HIV(IIIB) or the patient's own virus. The magnitude of the IFN-gamma response declined with disease progression, especially to autologous virus. T cell receptor (TCR) clonotypes of HIV(IIIB) and autologous virus-responding cells were determined by sequencing TCR beta chain variable (TCRBV) genes. In two of three asymptomatic donors, the dominant clonotypes overlapped, whereas in five symptomatic patients, the TCR clonotypes responding to HIV(IIIB) virus were completely different from those responding to autologous virus. Moreover, in cytolytic assays, T cell lines derived from IFN-gamma(+) cells responding to lab-adapted or autologous virus cross-recognized target cells infected with either virus in asymptomatic subjects with shared TCR clonotypes but not in progressors with differing clonotypes. Therefore, in advanced-stage patients, viral-specific CD8 T cells recognizing consensus epitopes persist from an earlier response but no longer effectively recognize autologous virus.

CD8-Positive T-Lymphocytes↗