A heterogeneous nuclear ribonucleoprotein A/B-related protein binds to single-stranded DNA near the 5' end or within the genome of feline parvovirus and can modify virus replication.
Phage display of cDNA clones prepared from feline cells was used to identify host cell proteins that bound to DNA-containing feline panleukopenia virus (FPV) capsids but not to empty capsids. One gene found in several clones encoded a heterogeneous nuclear ribonucleoprotein (hnRNP)-related protein (DBP40) that was very similar in sequence to the A/B-type hnRNP proteins. DBP40 bound specifically to oligonucleotides representing a sequence near the 5' end of the genome which is exposed on the outside of the full capsid but did not bind most other terminal sequences. Adding purified DBP40 to an in vitro fill-in reaction using viral DNA as a template inhibited the production of the second strand after nucleotide (nt) 289 but prior to nt 469. DBP40 bound to various regions of the viral genome, including a region between nt 295 and 330 of the viral genome which has been associated with transcriptional attenuation of the parvovirus minute virus of mice, which is mediated by a stem-loop structure of the DNA and cellular proteins. Overexpression of the protein in feline cells from a plasmid vector made them largely resistant to FPV infection. Mutagenesis of the protein binding site within the 5' end viral genome did not affect replication of the virus.
Wang
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James A. Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Parrish
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002415:Cats; D002460:Cell Line; D002645:Chickens; D004261:DNA Replication; D018076:DNA, Complementary; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D028301:Feline Panleukopenia Virus / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D016679:Genome, Viral; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
D018076:DNA, Complementary; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; C444244:hnRNP A-B related protein, cat