PMID- 10189358
OWN - NLM
STAT- MEDLINE
DCOM- 19990505
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 84
IP  - 6
DP  - 1999 Apr 2
TI  - Viral myocarditis: identification of five differentially expressed genes in
      coxsackievirus B3-infected mouse heart.
PG  - 704-12
AB  - Differences in host susceptibility to viral myocarditis caused by a given strain 
      of coxsackievirus B3 (CVB3) are known to be largely related to host genetic
      factors. Little is known, however, about the key genes that encode determinants
      (mediators) of myocarditis development or the nature of injury. To identify these
      genes and further understand the molecular mechanisms of the disease process, we 
      have used a murine model and the differential display technique to fingerprint
      mRNAs from CVB3-infected mouse hearts. Total RNA was extracted from hearts of 4- 
      and 10-week-old A/J(H-2(a)) mice at day 4 after CVB3 infection, and mRNAs were
      detected by reverse transcriptase-polymerase chain reaction and subsequently
      analyzed on polyacrylamide DNA sequencing gels. The differentially displayed
      bands were confirmed by Northern hybridization using the bands as cDNA probes.
      Twenty-eight upregulated or downregulated bands were selected from the sequencing
      gels; among these, 2 upregulated and 3 downregulated cDNA fragments were
      confirmed by Northern hybridization. DNA sequence analysis and GenBank searching 
      have determined that 4 of the 5 candidate genes are homologous to genes encoding 
      Mus musculus inducible GTPase, mouse mitochondrial hydrophobic peptide (a subunit
      of NADH dehydrogenase), mouse beta-globin, and Homo sapiens cAMP-regulated
      response element binding protein (CREB) binding protein (CBP), respectively. The 
      remaining candidate gene matches an unpublished cDNA clone, M musculus Nip21 mRNA
      (GenBank accession number, AF035207), which is homologous to human Nip2, a Bcl-2 
      binding protein. Our data suggest preliminarily that both structural and
      nonstructural genes are involved in myocarditis development. For the structural
      gene, beta-globin, we further confirmed its downregulation at the protein level
      by measuring the mean cell volume of red blood cells and found it was marginally 
      reduced in the CVB3-infected group (P<0.06), with no change in hemoglobin
      concentration. Cardiac myoglobin concentration was also measured and found to be 
      decreased (P<0.005), with a parallel decrease in total soluble protein in the
      CVB3-infected mouse myocardium (P<0.01). We also noted that the ratio of
      myoglobin to total protein was not significantly changed; this may be due to the 
      downregulation of additional genes in the host heart, a number being observed on 
      the differential display gels. The significant downregulation of beta-globin
      major gene expression in the heart may be relevant to impaired cardiac function
      in both the early and late postinfection period. The other identified
      nonstructural genes are known to be involved in regulation of gene expression,
      signal transduction pathways, and apoptotic cell death. The altered expression of
      structural and nonstructural genes may play important roles in the mediation of
      myocarditis development and perhaps other pathological processes in the heart.
FAU - Yang, D
AU  - Yang D
AD  - Department of Pathology and Laboratory Medicine, University of British
      Columbia-St Paul's Hospital, Vancouver, British Columbia, Canada.
      dyang@prl.pulmonary.ubc.ca
FAU - Yu, J
AU  - Yu J
FAU - Luo, Z
AU  - Luo Z
FAU - Carthy, C M
AU  - Carthy CM
FAU - Wilson, J E
AU  - Wilson JE
FAU - Liu, Z
AU  - Liu Z
FAU - McManus, B M
AU  - McManus BM
LA  - eng
SI  - GENBANK/AF071427
SI  - GENBANK/AF071428
SI  - GENBANK/AF071429
SI  - GENBANK/AF071430
SI  - GENBANK/AF071431
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Myoglobin)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Coxsackievirus Infections/*genetics/pathology
MH  - Enterovirus B, Human/*genetics
MH  - *Gene Expression Regulation, Viral
MH  - In Situ Hybridization
MH  - Mice
MH  - Mice, Inbred A
MH  - Myocarditis/*genetics/pathology/*virology
MH  - Myocardium/chemistry/metabolism
MH  - Myoglobin/metabolism
MH  - RNA, Viral/analysis
EDAT- 1999/04/03 00:00
MHDA- 1999/04/03 00:01
CRDT- 1999/04/03 00:00
PHST- 1999/04/03 00:00 [pubmed]
PHST- 1999/04/03 00:01 [medline]
PHST- 1999/04/03 00:00 [entrez]
AID - 10.1161/01.res.84.6.704 [doi]
PST - ppublish
SO  - Circ Res. 1999 Apr 2;84(6):704-12. doi: 10.1161/01.res.84.6.704.