The g5R (D250) Gene of African Swine Fever Virus Encodes a Nudix Hydrolase That Preferentially Degrades Diphosphoinositol Polyphosphates

Cartwright, Jared; Safrany, Stephen T.; Dixon, Linda K.; Darżynkiewicz, Edward; Stępiński, Janusz; Burke, Richard; McLennan, Alexander G.

doi:10.1128/jvi.76.3.1415-1421.2002

Cited by 41 publications

(37 citation statements)

References 26 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Iridoviruses and African swine fever virus each contain a protein with a mutT motif, although they otherwise have little sequence similarity with D9 or D10 (22,30). The African swine fever virus nudix hydrolase can cleave a wide range of nucleotide substrates, with a preference for diphosphoinositol polyphosphates, but is unable to cleave RNA cap analogs (11). A subset of cellular nudix hydrolases has been shown to mediate mRNA decapping, leading to the subsequent degradation of the cleaved transcript (16,36).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Vaccinia Virus Mutant with a Deletion of the D10R Gene Encoding a Putative Negative Regulator of Gene Expression

Parrish

Moss

2006

J Virol

105

View full text Add to dashboard Cite

The D9 and D10 proteins of vaccinia virus are 25% identical to each other, contain a mutT motif characteristic of nudix hydrolases, and are conserved in all sequenced poxviruses. Previous studies indicated that overexpression of D10 and, to a lesser extent, D9 decreased the levels of capped mRNAs and their translation products. Here, we further characterized the D10 protein and showed that only trace amounts are associated with purified virions and that it is expressed exclusively at late times after vaccinia virus infection. A viable deletion mutant (v⌬D10) produced smaller plaques and lower virus yields than either wild-type virus or a D9R deletion mutant (v⌬D9). Purified v⌬D10 virions appeared normal by microscopic examination and biochemical analysis but produced 6-to 10-fold-fewer plaques at the same concentration as wild-type or v⌬D9 virions. When 4 PFU per cell of wild-type or v⌬D9 virions or equal numbers of v⌬D10 virions were used for inoculation, nearly all cells were infected in each case, but viral early and late transcription was initiated more slowly in v⌬D10-infected cells than in the others. However, viral early transcripts accumulated to higher levels in v⌬D10-infected cells than in cells infected with the wild type or v⌬D9. In addition, viral early and late mRNAs and cellular actin mRNA persisted longer in v⌬D10-infected cells than in others. Furthermore, analysis of pulse-labeled proteins indicated prolonged synthesis of cellular and viral early proteins. These results are consistent with a role for D10 in regulating RNA levels in poxvirus-infected cells.Vaccinia virus (VACV), the most extensively studied member of the Poxviridae family, contains a large double-stranded DNA genome encoding approximately 200 proteins. Replication occurs in the cytoplasm and is orchestrated in a programmed manner, with sequential transcription of early-, intermediate-, and late-stage genes (25). Numerous positive regulatory factors have been identified, notably the proteins required for stage-specific transcription in conjunction with the viral DNA-dependent RNA polymerase (for a review, see reference 8). The changes in total viral early, intermediate, and late RNA levels, however, suggest the deployment of negative, as well as positive, regulators (3). Indeed, the speed at which RNA levels change can only be explained if viral RNAs have very short half-lives, as was proposed nearly 40 years ago (26, 31). The accelerated turnover of cellular mRNAs during VACV infection (9,19,20,29) might occur by a related or identical degradation mechanism.A putative negative regulator of gene expression was identified in a transfection-based DNA library screen that was successfully used to find activators of VACV late transcription (21, 32). The inhibitory activity was mapped primarily to the D10R gene of VACV, with the D9R gene contributing more modestly to the effect. (Note: VACV genes are designated with a capital letter that describes the HindIII fragment containing the open reading frame, followed by a number that corresp...

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of a Vaccinia Virus Mutant with a Deletion of the D10R Gene Encoding a Putative Negative Regulator of Gene Expression

Parrish

Moss

2006

J Virol

105

View full text Add to dashboard Cite

show abstract

“…ASFV encodes a guanylyltransferase (pNP868R) similar to the heterodimeric vaccinia virus capping enzyme large subunit that performs both triphosphatase and guanylyltransferase activities; however, it is not known if ASFV proteins have the two additional capping activities and poly(A) polymerase functions (Pena et al 1993;Shuman 1989;Yanez 1995). An ASFV-encoded Nudix (nucleoside diphosphate X) hydrolase (pD250R), while sharing sequence similarity with the vaccinia virus D10 protein that affects transcript stability through removal of mRNA cap structures, exhibits higher hydrolytic activity toward diphosphoinositol polyphosphates and dinucleoside polyphosphates than toward cap analogs in vitro (Cartwright et al 2002;Parrish et al 2007).…”

Section: Viral Transcriptionmentioning

confidence: 99%

African Swine Fever Virus

Tulman

Delhon

et al. 2009

Current Topics in Microbiology and Immunology

132

117

View full text Add to dashboard Cite

African swine fever virus (ASFV) is a large, intracytoplasmicallyreplicating DNA arbovirus and the sole member of the family Asfarviridae . It is the etiologic agent of a highly lethal hemorrhagic disease of domestic swine and therefore extensively studied to elucidate the structures, genes, and mechanisms affecting viral replication in the host, virus-host interactions, and viral virulence. Increasingly apparent is the complexity with which ASFV replicates and interacts with the host cell during infection. ASFV encodes novel genes

show abstract

“…These have been described previously (see references in Supplementary Table S1). Four other conserved enzymes, a prenyl transferase, ubiquitin conjugating enzyme, protein kinase and nudix hydrolase, may either be involved in regulating the virus replication cycle or in modulating host cell function (Alejo et al, 1997;Baylis et al, 1993a;Cartwright et al, 2002;Hingamp et al, 1992). Eight conserved ORFs encode proteins involved in regulating host cell activities.…”

Section: Asfv Genome Comparisonmentioning

confidence: 99%

Comparison of the genome sequences of non-pathogenic and pathogenic African swine fever virus isolates

Chapman

Tcherepanov

Upton

et al. 2008

Journal of General Virology

Self Cite

258

256

View full text Add to dashboard Cite

The genomic coding sequences, apart from the inverted terminal repeats and cross-links, have been determined for two African swine fever virus (ASFV) isolates from the same virus genotype, a non-pathogenic isolate from Portugal, OURT88/3, and a highly pathogenic isolate from West Africa, Benin 97/1. These genome sequences were annotated and compared with that of a tissue culture-adapted isolate, BA71V. The genomes range in length between 170 and 182 kbp and encode between 151 and 157 open reading frames (ORFs). Compared to the Benin 97/1 isolate, the OURT88/3 and BA71V isolates have deletions of 8–10 kbp that encode six copies of the multigene family (MGF) 360 and either one MGF 505/530 copy in the BA71V or two copies in the OURT88/3 isolate. The BA71V isolate has a deletion, close to the right end of the genome, of 3 kbp compared with the other isolates. The five ORFs in this region include an additional copy of an ORF similar to that encoding the p22 virus structural protein. The OURT88/3 isolate has interruptions in ORFs that encode a CD2-like and a C-type lectin protein. Variation between the genomes is observed in the number of copies of five different MGFs. The 109 non-duplicated ORFs conserved in the three genomes encode proteins involved in virus replication, virus assembly and modulation of the host's defences. These results provide information concerning the genetic variability of African swine fever virus isolates that differ in pathogenicity.

show abstract

The g5R (D250) Gene of African Swine Fever Virus Encodes a Nudix Hydrolase That Preferentially Degrades Diphosphoinositol Polyphosphates

Cited by 41 publications

References 26 publications

Characterization of a Vaccinia Virus Mutant with a Deletion of the D10R Gene Encoding a Putative Negative Regulator of Gene Expression

Characterization of a Vaccinia Virus Mutant with a Deletion of the D10R Gene Encoding a Putative Negative Regulator of Gene Expression

African Swine Fever Virus

Comparison of the genome sequences of non-pathogenic and pathogenic African swine fever virus isolates

Contact Info

Product

Resources

About