TY - JOUR
T1 - MiRNA-124 is a link between measles virus persistent infection and cell division of human neuroblastoma cells
T2 - PLoS One
AU - Naaman, H.
AU - Rall, G.
AU - Matullo, C.
AU - Veksler-Lublinsky, I.
AU - Shemer-Avni, Y.
AU - Gopas, J.
N1 - 1932-6203 Naaman, Hila Rall, Glenn Matullo, Christine Veksler-Lublinsky, Isana Shemer-Avni, Yonat Gopas, Jacob ORCID: http://orcid.org/0000-0001-9289-8898 Journal Article United States PLoS One. 2017 Oct 26;12(10):e0187077. doi: 10.1371/journal.pone.0187077. eCollection 2017.
PY - 2017
Y1 - 2017
N2 - Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells. Persistent MV infection was accompanied by differences in the expression profile and levels of several host cell-encoded microRNAs as compared to uninfected cells. MV persistence infection of a human neuroblastoma cell line (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell division but not cell death. By contrast, acute MV infection of UKF-NB cells did not result in increased miRNA-124 levels or CDK6 reduction. Ectopic overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells, causing cell death; implying that miRNA-124 over expression can sensitize cells to death only in the presence of MV persistent infection. To determine if miRNA-124 directly contributes to the establishment of MV persistence, UKF-NB cells overexpressing miRNA-124 were acutely infected, resulting in establishment of persistently infected colonies. We propose that miRNA-124 triggers a CDK6-dependent decrease in cell proliferation, which facilitates the establishment of MV persistence in neuroblastoma cells. To our knowledge, this is the first report to describe the role of a specific miRNA in MV persistence.
AB - Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells. Persistent MV infection was accompanied by differences in the expression profile and levels of several host cell-encoded microRNAs as compared to uninfected cells. MV persistence infection of a human neuroblastoma cell line (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell division but not cell death. By contrast, acute MV infection of UKF-NB cells did not result in increased miRNA-124 levels or CDK6 reduction. Ectopic overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells, causing cell death; implying that miRNA-124 over expression can sensitize cells to death only in the presence of MV persistent infection. To determine if miRNA-124 directly contributes to the establishment of MV persistence, UKF-NB cells overexpressing miRNA-124 were acutely infected, resulting in establishment of persistently infected colonies. We propose that miRNA-124 triggers a CDK6-dependent decrease in cell proliferation, which facilitates the establishment of MV persistence in neuroblastoma cells. To our knowledge, this is the first report to describe the role of a specific miRNA in MV persistence.
KW - Apoptosis/genetics Cell Division/genetics Cell Line, Tumor Cyclin-Dependent Kinase 6/metabolism Down-Regulation Humans Measles/genetics/pathology MicroRNAs/genetics Neuroblastoma/pathology
UR - http://www.scopus.com/inward/record.url?scp=85032478714&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0187077
DO - 10.1371/journal.pone.0187077
M3 - Article
SN - 1932-6203
VL - 12
SP - e0187077
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e0187077
ER -