Measles virus induces cell-type specific changes in gene expression

Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Virology (Impact Factor: 3.32). 07/2008; 375(2):321-30. DOI: 10.1016/j.virol.2008.02.015
Source: PubMed


Measles virus (MV) causes various responses including the induction of immune responses, transient immunosuppression and establishment of long-lasting immunity. To obtain a comprehensive view of the effects of MV infection on target cells, DNA microarray analyses of two different cell-types were performed. An epithelial (293SLAM; a 293 cell line stably expressing SLAM) and lymphoid (COBL-a) cell line were inoculated with purified wild-type MV. Microarray analyses revealed significant differences in the regulation of cellular gene expression between these two different cells. In 293SLAM cells, upregulation of genes involved in the antiviral response was rapidly induced; in the later stages of infection, this was followed by regulation of many genes across a broad range of functional categories. On the other hand, in COBL-a cells, only a limited set of gene expression profiles was modulated after MV infection. Since it was reported that V protein of MV inhibited the IFN signaling pathway, we performed a microarray analysis using V knockout MV to evaluate V protein's effect on cellular gene expression. The V knockout MV displayed a similar profile to that of parental MV. In particular, in COBL-a cells infected with the virus, no alteration of cellular gene expression, including IFN signaling, was observed. Furthermore, IFN signaling analyzed in vitro was completely suppressed by MV infection in the COBL-a cells. These results reveal that MV induces different cellular responses in a cell-type specific manner. Microarray analyses will provide us useful information about potential mechanisms of MV pathogenesis.

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Available from: Chieko Kai
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    • "Construction of the mammalian expression plasmids encoding the MV-HL N gene (pCAG-MV-N), P (Hagiwara et al., 2008) and V (Sato et al., 2008) was described previously. To construct expression plasmids encoding the MV C and M proteins, cDNAs were amplified by PCR (Phusion; Finnzymes, Espoo, Finland) from pMV-HL (7+) encoding the full-length genome cDNA of MV-HL (Terao-Muto et al., 2008), with specific primers matching the ORF extremities. "
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    ABSTRACT: Measles virus (MV) belongs to the genus Morbillivirus of the family Paramyxoviridae. A number of paramyxoviruses inhibit host interferon (IFN) signaling pathways in host immune systems by various mechanisms. Inhibition mechanisms have been described for many paramyxoviruses. Although there are inconsistencies among previous reports concerning MV, it appears that P/V/C proteins interfere with the pathways. In this study, we confirmed the effects of MV P gene products of a wild MV strain on IFN pathways and examined that of other viral proteins on it. Interestingly, we found that N protein acts as an IFN-α/β and γ-antagonist as strong as P gene products. We further investigated the mechanisms of MV-N inhibition, and revealed that MV-N blocks the nuclear import of activated STAT without preventing STAT and Jak activation or STAT degradation, and that the nuclear translocation of MV-N is important for the inhibition. The inhibitory effect of the N protein was observed as a common feature of other morbilliviruses. The results presented in this report suggest that N protein of MV as well as P/V/C proteins is involved in the inhibition of host IFN signaling pathways.
    Full-text · Article · Mar 2012 · Virology
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    • "The C protein of the MV used in these studies blocks IFN induction induced by cytoplasmic dsRNA, but not that which is induced via TLRs (Boxer, E.L. and Baron, M.D., unpublished), so the mechanisms involved appear to be fundamentally different. RPV has evolved mechanisms to suppress IFN induction by a number of different pathways, while MV seems to have adopted a strategy that allows it to replicate, in humans at least, in the face of a strong type 1 IFN response in at least some cell types (Sato et al., 2008; Zilliox et al., 2006). Such a difference in strategy would have implications for the risk of MV crossing into animal populations, or the risk of animal morbilliviruses crossing into human populations if MV is eradicated and vaccination stopped. "
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    ABSTRACT: The morbilliviruses are a closely related genus which are very similar in their sequences and share a common receptor, but nevertheless show significant restriction in the host species in which they cause disease. One contribution to this restriction might be the nature of the hosts' responses to infection. We have used microarrays to study the changes in the transcriptome of bovine dendritic cells after infection with wild-type (pathogenic) and vaccine (apathogenic) strains of rinderpest virus (RPV), a bovine pathogen, and a wild-type isolate of measles virus (MV), a morbillivirus that causes disease only in humans and some other primates. We found that, as previously observed in human cells, MV induces a rapid interferon response, while that induced by RPV was delayed and much reduced in magnitude. Pathogenic and apathogenic RPV also showed significant differences, with the latter inducing a slightly higher interferon response as well as significant effects on transcription of genes involved in cell cycle regulation.
    Full-text · Article · Oct 2009 · Virology
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    • "DNA microarray technology, in combination with bioinformatics , has proved to be a very efficient, highthroughput tool and offers great advantages in the study of genomic expression profiles of cells. Widely used for human, mouse and rat gene expression studies, highdensity gene arrays have been used increasingly to evaluate the status of host gene expression following infection by viruses such as human immunodeficiency virus (HIV) (Solis et al., 2006), dengue virus (Fink et al., 2007), measles virus (Sato et al., 2008), Newcastle disease virus (Munir et al., 2005), rabies virus (Ubol et al., 2005) and simian immunodeficiency virus (George et al., 2003). "
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    ABSTRACT: Classical swine fever (CSF), caused by a virus of the same name (CSFV), is a highly contagious swine pyrexic disease featuring extensive haemorrhagic lesions and leukopenia, but little is known about the molecular mechanisms of its pathogenesis. To gain insight into the interaction between the virus and host cells, microarray analyses were performed to detect alterations in genomic expression of pig peripheral blood leukocytes (PBLs) following CSFV infection. Three healthy pigs were inoculated with a lethal dose of highly virulent CSFV strain Shimen. PBLs were isolated at the onset of typical clinical signs and total RNA was subjected to microarray analyses with Affymetrix Porcine Genome Array GeneChips. Of all 20,201 pig genes arrayed in the chip, 1745 showed altered expression (up- or downregulation) after infection. These were classified into eight functional groups, relating to cell proliferation (3.6%), immune response (2.1%), apoptosis (1.4%), kinase activity (1.4%), signal transduction (1.4%), transcription (0.7%), receptor activity (0.7%) and cytokines/chemokines (0.4%). The remaining 88.3% of genes had unknown functions. Alterations in genomic expression were confirmed by real-time RT-PCR of selected cellular genes and Western blotting of annexin 2, a cellular protein relating to virus infection. The observed expression changes of numerous genes involved in immune and inflammatory responses and in the apoptosis process indicate that CSFV has developed sophisticated mechanisms to cause leukopenia in infected pigs. These data provide a basis for exploring the molecular pathogenesis of CSFV infection through an understanding of the interaction between viral and cellular components.
    Full-text · Article · Apr 2009 · Journal of General Virology
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