Disease relevance of EhV2gp58

• Furthermore, nucleolar retargeting of the ORF57 mutant was achieved by the incorporation of the HIV-1 Rev nucleolar localization signal, and analysis demonstrated that this modification was sufficient to restore viral mRNA nuclear export [1].
• Structural and Functional Analyses of Kaposi Sarcoma-associated Herpesvirus ORF57 Nuclear Localization Signals in Living Cells [2].
• Kaposi's sarcoma-associated herpesvirus lytic gene ORF57 is essential for infectious virion production [3].
• Conversely, ORF57 did not rescue an SM-null recombinant EBV, indicating the existence of virus-specific functions for the ORF57 family of genes [3].
• An ORF57 homolog is present in all known human herpesviruses and many animal herpesviruses [3].

High impact information on EhV2gp58

• Intriguingly, point mutations that ablate ORF57 nucleolar localization lead to a failure of ORF57-mediated viral mRNA nuclear export [1].
• Thus, the three NLSs identified in ORF57 provide at least two functions, nuclear localization of ORF57 and up-regulation of ORF59 expression [2].
• We propose that ORF57-mediated RNA export may use different export factors to accommodate the KSHV-infected host cell environments, for example, in B-cells or endothelial cells and during the different phases of lytic virus replication [4].
• Targeted disruption of Kaposi's sarcoma-associated herpesvirus ORF57 in the viral genome is detrimental for the expression of ORF59, K8alpha, and K8.1 and the production of infectious virus [5].
• The ectopic expression of ORF57 partially complemented the replication deficiency of the disrupted KSHV genome and the expression of the lytic gene ORF59 [5].

Chemical compound and disease context of EhV2gp58

• The disrupted viral genome, Bac36-Delta57, did not express ORF57, ORF59, K8alpha, K8.1, or a higher level of polyadenylated nuclear RNA after butyrate induction and could not be induced to produce infectious viruses in the presence of valproic acid, a histone deacetylase inhibitor and a novel KSHV lytic cycle inducer [5].

Biological context of EhV2gp58

• The Epstein-Barr virus (EBV) homolog of ORF57, SM, was unable to rescue lytic KSHV virion production, although EBV SM does enhance KSHV lytic gene expression from the ORF57-null mutant [3].
• These data indicate that ORF 57 is a powerful pleiotropic effector that can act on several posttranscriptional levels to modulate the expression of viral genes in infected cells [6].
• ORF57 enhances expression of reporter genes posttranscriptionally in vitro and may synergize with transcription factors to enhance gene transcription [3].
• Here we identify and characterize a DNA binding site for the ORF50 protein that is shared by the promoters of two delayed early genes (ORF57 and K-bZIP) [7].
• ORF56 was transcribed from two transcription start sites, nucleotides (nt) 78994 (minor) and 79075 (major), but selected the same poly(A) signal as ORF57 for RNA polyadenylation [8].

Regulatory relationships of EhV2gp58

• The expression from some (e.g., nut-1) but not all (e.g., tk) ORF 50-responsive promoters can be synergistically enhanced by coexpression of ORF 50 and ORF 57 [6].

Analytical, diagnostic and therapeutic context of EhV2gp58

• Co-immunoprecipitations with extracts of KSHV-infected cells showed that ORF57 and ORF50 proteins were present in the same complex [9].

References