Insertion of a sequence encoding light chain 3 of microtubule-associated proteins 1A and 1B in a pestivirus genome: connection with virus cytopathogenicity and induction of lethal disease in cattle.
Pestiviruses represent the first RNA viruses for which recombination with cellular protein-coding sequences has been reported. As a result of such recombinations cytopathogenic (cp) pestiviruses can develop from noncytopathogenic (noncp) viruses. In the case of bovine viral diarrhea virus (BVDV), the generation of cp mutants is linked to the induction of the lethal syndrome mucosal disease (MD) in cattle. The cp BVDV JaCP was isolated from an animal which had come down with MD. The genome of JaCP contains a novel kind of cellular insertion (LC3*) which is flanked by duplicated pestivirus sequences. Neither insertion nor duplication is present in the genome of the accompanying noncp virus JaNCP. As part of the viral polyprotein, the insertion in the JaCP genome is translated into a polypeptide almost identical to a fragment of light chain 3, a subunit of the microtubule-associated proteins 1A and 1B from the rat. Transient-expression studies revealed that the LC3* sequence is able to induce an additional cleavage of the viral polyprotein. The respective cleavage occurs directly downstream of the LC3*-encoded sequence and is not dependent on the NS3 serine protease. Insertion of LC3* into an infectious noncp pestivirus cDNA clone without duplicated viral sequences resulted in recovery of a defective cp virus able to replicate only in the presence of a noncp helper virus. In contrast, introduction of both insertion and duplication led to an autonomously replicating cp virus.
Meyers
G
G
Department of Clinical Virology, Federal Research Centre for Virus Diseases of Animals, Tübingen, Germany. gregor.meyers@tue.bfav.de
Stoll
D
D
Gunn
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000401:mortality / Q000821:virology*; D002417:Cattle; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D001908:Diarrhea Viruses, Bovine Viral / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D016679:Genome, Viral; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010447:Peptide Hydrolases; D014176:Protein Biosynthesis; D020365:RNA Helicases; D012367:RNA, Viral; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014764:Viral Proteins / Q000032:analysis; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D008869:Microtubule-Associated Proteins; D010447:Peptide Hydrolases; D020365:RNA Helicases; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C490546:Map1a protein, rat; C085284:microtubule-associated protein 1B; C086730:p80 protein, bovine viral diarrhea virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases