Complete Genomic Sequence and Phylogenetic Analysis of the Lactate Dehydrogenase-Elevating Virus (LDV)

Abstract

The apparently complete sequence of the RNA genome of the neurovirulent isolate of lactate dehydrogenase-elevating virus (LDV-C) has been determined. The LDV-C genome is at least 14,222 nucleotides in length and contains eight open reading frames (ORFs). ORF 1a, which encodes a protein of 242.8 kDa and is located at the 5' end of the genome, contains at least two putative papain-like cysteine protease domains, and one putative chymotrypsin-like serine protease domain. This ORF terminates with a UAG stop codon that can be bypassed if a -1 frameshift occurs. The frameshift region consists of a heptanucleotide "slippery" sequence, 5'-UUUAAAC-3', followed by a putative pseudoknot. ORF 1b encodes a protein of 155.4 kDa containing, in its N-terminal portion, an RNA-dependent RNA polymerase and an RNA helicase domain separated by a Zn finger domain. Another domain of unknown function that is also conserved in coronaviruses and toroviruses is located at the C-terminus of the ORF 1b product. Three cleavage sites in the ORF 1a polyprotein and three in the ORF 1b polyprotein were predicted for the chymotrypsin-like protease and tentatively delimit the mature nonstructural proteins of LDV. Six small, overlapping 3' ORFs (ORFs 2 through 7) encode proteins with calculated sizes of 25.8, 21.6, 19.8, 23.9, 18.9, and 12.3 kDa. ORF 7 encodes the virion nucleocapsid protein Vp-1, while ORF 6 encodes the nonglycosylated envelope protein Vp2. ORFs 5, 4, 3, and 2 each encode glycoproteins which may be virion envelope proteins. LDV is closely related to equine arteritis virus, Lelystad virus (LV), and simian hemorrhagic fever virus. These four viruses belong to a new group of positive-strand RNA viruses and are related to coronaviruses and toroviruses.

Complete genome structure and phylogenetic analysis of little cherry virus, a mealybug-transmissible closterovirus.

“…2). Similar variability of the Ph1 amino acids has been described for the leader PCP of arteriviruses and coronaviruses, which have Gly\Gly, Gly\Ala, Gly\Val or Gly\Tyr dipeptides as cleavage sites (Godeny et al, 1993 ;Dong & Baker, 1994 ;den Boon et al, 1995).…”

Characterization of Emerging European-Like Porcine Reproductive and Respiratory Syndrome Virus Isolates in the United States

“…NSP2 has been shown to be variable in length among sequenced isolates of arteriviruses (1,36,39,61). PRRSV type 1 strain LV NSP2 is 861 aa in length while type 2 strains have an additional 100 aa or more, and lactate dehydrogenase-elevating virus and EAV encode NSP2 proteins which are 733 and 401 aa in length, respectively (1,20,36,82,85). Snijder et al (66) found that the NSP2 protein of EAV was involved in proteolysis of replicase precursors and membrane association of the virus replication complex, but no confirming work has been reported for other arteriviruses.…”

Toroviruses: replication, evolution and comparison with other members of the coronavirus-like superfamily

“…Subsequently, the CVL group was expanded to include the arteriviruses, which also produce a 3'-coterminal nested set of mRNAs. The protein-coding regions of the genomes of EAV (den Boon et al, 1991 b), LDV (Kuo et al, 1991 ;Godeny et al, 1990Godeny et al, , 1993Chen et al, 1993) and LV (Meulenberg et al, 1993a;Conzelmann et al, 1993) have now been sequenced completely. Although arterivirus replicase genes are considerably smaller (9.5 to 12 kb) than their toro-and coronavirus counterparts, they also contain two ORFs, the downstream ones of which are expressed by ribosomal frameshifting.…”