File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

postgraduate thesis: Enterovirus 71 directly infects human natural killer cells and induces cell apoptosis

TitleEnterovirus 71 directly infects human natural killer cells and induces cell apoptosis
Authors
Issue Date2011
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Liang, H. [梁湖沂]. (2011). Enterovirus 71 directly infects human natural killer cells and induces cell apoptosis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4732943
AbstractEnterovirus 71 (EV71) belongs to the Enterovirus genus of the family Picornaviridae and is the major causative agent of hand, foot and mouth disease (HFMD). Although clinical manifestations of HFMD are usually mild and self-limiting, severe HFMD patients suffer from a diverse array of neurological diseases and sometimes these diseases are fatal. HFMD usually occurs in young children and gradually becomes a new threaten in Asia. Unfortunately, effective EV71 vaccine is not available to date and alternative treatments are still in debate. This is partially due to the lack of understanding of EV71 pathogenesis and host immune responses against EV71. Natural killer (NK) cells are key effector cells in host antiviral activities by directly killing viral-infected cells and producing cytokines and chemokines, especially in early phase of viral infection. After enteroviruses infection, NK cells were one of the most abundant cell types in the inflammatory infiltrate, and appeared to limit both enteroviruses replication and virus-induced disease in experimental mice model. However, role of human NK cells during EV71 infection, especially the direct interaction between EV71 and human NK cells, was not studied extensively. Clinical observation manifested that patients with severe EV71 infection have marked diminished NK cells in peripheral blood. Therefore we hypothesized that EV71 might directly target human NK cells as one of its immunoevasion strategies. Here, we demonstrated for the first time that fresh primary human NK cells were susceptible to EV71 infection. By flow cytometry and florescence microscope, EV71 capsid protein VP1 was able to be detected in viral-infected NK cells as soon as 6 hours after infection and peaked at 24 hour after infection. In the same time, EV71 viral RNA was detected by quantitative RT-PCR and the viral copies increased from 6 hour onwards to peak at 12 hours after infection. We further demonstrated the infectious entry of EV71 in human NK cells was depended on clathrin-mediated endocytosis. Next, we illustrated that EV71 infection could trigger NK cells apoptosis as evidenced by increased Annexin V+, PI+, and activated caspase 3+ cells in EV71-treated NK cells. We further proved that the cytotoxicity of NK cells was inhibited by EV71 infection and this inhibition might not be related with down-regulation of NKp46, but may be related to the increased apoptosis. In conclusion, our data suggested that EV71 might directly target and kill NK cells as a strategy to evade human innate immunity, which might facilitate virus replication, transmission and then contribute to viral-related pathogenesis.
DegreeMaster of Philosophy
SubjectApoptosis
Enteroviruses
Killer cells
Dept/ProgramPaediatrics and Adolescent Medicine
Persistent Identifierhttp://hdl.handle.net/10722/208428

 

DC FieldValueLanguage
dc.contributor.authorLiang, Huyi-
dc.contributor.author梁湖沂-
dc.date.accessioned2015-03-09T02:47:50Z-
dc.date.available2015-03-09T02:47:50Z-
dc.date.issued2011-
dc.identifier.citationLiang, H. [梁湖沂]. (2011). Enterovirus 71 directly infects human natural killer cells and induces cell apoptosis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4732943-
dc.identifier.urihttp://hdl.handle.net/10722/208428-
dc.description.abstractEnterovirus 71 (EV71) belongs to the Enterovirus genus of the family Picornaviridae and is the major causative agent of hand, foot and mouth disease (HFMD). Although clinical manifestations of HFMD are usually mild and self-limiting, severe HFMD patients suffer from a diverse array of neurological diseases and sometimes these diseases are fatal. HFMD usually occurs in young children and gradually becomes a new threaten in Asia. Unfortunately, effective EV71 vaccine is not available to date and alternative treatments are still in debate. This is partially due to the lack of understanding of EV71 pathogenesis and host immune responses against EV71. Natural killer (NK) cells are key effector cells in host antiviral activities by directly killing viral-infected cells and producing cytokines and chemokines, especially in early phase of viral infection. After enteroviruses infection, NK cells were one of the most abundant cell types in the inflammatory infiltrate, and appeared to limit both enteroviruses replication and virus-induced disease in experimental mice model. However, role of human NK cells during EV71 infection, especially the direct interaction between EV71 and human NK cells, was not studied extensively. Clinical observation manifested that patients with severe EV71 infection have marked diminished NK cells in peripheral blood. Therefore we hypothesized that EV71 might directly target human NK cells as one of its immunoevasion strategies. Here, we demonstrated for the first time that fresh primary human NK cells were susceptible to EV71 infection. By flow cytometry and florescence microscope, EV71 capsid protein VP1 was able to be detected in viral-infected NK cells as soon as 6 hours after infection and peaked at 24 hour after infection. In the same time, EV71 viral RNA was detected by quantitative RT-PCR and the viral copies increased from 6 hour onwards to peak at 12 hours after infection. We further demonstrated the infectious entry of EV71 in human NK cells was depended on clathrin-mediated endocytosis. Next, we illustrated that EV71 infection could trigger NK cells apoptosis as evidenced by increased Annexin V+, PI+, and activated caspase 3+ cells in EV71-treated NK cells. We further proved that the cytotoxicity of NK cells was inhibited by EV71 infection and this inhibition might not be related with down-regulation of NKp46, but may be related to the increased apoptosis. In conclusion, our data suggested that EV71 might directly target and kill NK cells as a strategy to evade human innate immunity, which might facilitate virus replication, transmission and then contribute to viral-related pathogenesis.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshApoptosis-
dc.subject.lcshEnteroviruses-
dc.subject.lcshKiller cells-
dc.titleEnterovirus 71 directly infects human natural killer cells and induces cell apoptosis-
dc.typePG_Thesis-
dc.identifier.hkulb4732943-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePaediatrics and Adolescent Medicine-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4732943-
dc.date.hkucongregation2012-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats