Positive and negative regulation of adenovirus infection by CAR-like soluble protein, CLSP.
Coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin (Ig) superfamily and a component of epithelial tight junction. CAR also functions as a primary receptor for coxsackievirus B and adenovirus (Ad) infection. In this study, we report the identification of a novel protein, CAR-like soluble protein (CLSP), which is closely related to CAR. Mouse CLSP (mCLSP) was composed of 390 amino acids, including three Ig domains, and showed strong homology to the IgV domain of CAR. Interestingly, mCLSP lacks a transmembrane domain, indicating that this is a soluble protein. mCLSP mRNA was detected primarily in the brain and ovary. When mCLSP cDNA was introduced into SK HEP-1 cells, which were known to be CAR positive and easily infected with Ad vector, the infection with Ad vector was severely inhibited. On the other hand, mCLSP promoted the infection with Ad vector in CAR-negative NIH3T3 cells. Furthermore, recombinant CLSP directly bound to Ad and inhibited the Ad vector-mediated transduction in SK HEP-1 cells. Computational analysis for a genome database showed that the CLSP gene is rodent-specific, and that human and bovine lack this gene. These results suggest that CLSP may play a role in the antiviral defense of the host in rodent animals.
Kawabata
K
K
Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan.
Tashiro
K
K
Sakurai
F
F
Osada
N
N
Kusuda
J
J
Hayakawa
T
T
Yamanishi
K
K
Mizuguchi
H
H
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D002645:Chickens; D019295:Computational Biology; D030541:Databases, Genetic; D029968:Escherichia coli Proteins / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010445:Peptide Elongation Factors / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics; D035602:Transcriptional Elongation Factors; D014161:Transduction, Genetic; D014162:Transfection / Q000379:methods
C525513:CLSP protein, mouse; D029968:Escherichia coli Proteins; D010445:Peptide Elongation Factors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C068727:nusA protein, E coli