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The immunogenic glycoprotein gp35-37 of human herpesvirus 8 is encoded by open reading frame K8.1.

ABSTRACT: Human herpesvirus 8 (HHV-8) is likely to be involved in the pathogenesis of Kaposi's sarcoma (KS) and body cavity-based lymphomas (BCBLs). The HHV-8 genome is primarily in a latent state in BCBL-derived cell lines like BCBL-1, but lytic replication can be induced by phorbol esters (R. Renne, W. Zhang, B. Herndier, M. McGrath, N. Abbey, D. Kedes, and D. E. Ganem, Nat. Med. 2:342-346, 1996). A 35- to 37-kDa glycoprotein (gp35-37) is the polypeptide most frequently and intensively recognized by KS patient sera on Western blots with induced BCBL-1 cells. Its apparent molecular mass is reduced to 30 kDa by digestion with peptide-N-glycosidase F. By searching the known HHV-8 genomic sequence for open reading frames (ORF) with the potential to encode such a glycoprotein, an additional, HHV-8-specific reading frame was identified adjacently to ORF K8. This ORF, termed K8.1, was found to be transcribed primarily into a spliced mRNA encoding a glycoprotein of 228 amino acids. Recombinant K8.1 was regularly recognized by KS patient sera in Western blots, and immunoaffinity-purified antibodies to recombinant K8.1 reacted with gp35-37. This shows that the immunogenic gp35-37 is encoded by HHV-8 reading frame K8.1, which will be a useful tool for studies of HHV-8 epidemiology and pathogenesis.

SUBMITTER: Raab MS

PROVIDER: S-EPMC109880 | biostudies-literature | 1998 Aug

REPOSITORIES: biostudies-literature

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The immunogenic glycoprotein gp35-37 of human herpesvirus 8 is encoded by open reading frame K8.1.

Raab M S MS Albrecht J C JC Birkmann A A Yağuboğlu S S Lang D D Fleckenstein B B Neipel F F

Journal of virology 19980801 8

Human herpesvirus 8 (HHV-8) is likely to be involved in the pathogenesis of Kaposi's sarcoma (KS) and body cavity-based lymphomas (BCBLs). The HHV-8 genome is primarily in a latent state in BCBL-derived cell lines like BCBL-1, but lytic replication can be induced by phorbol esters (R. Renne, W. Zhang, B. Herndier, M. McGrath, N. Abbey, D. Kedes, and D. E. Ganem, Nat. Med. 2:342-346, 1996). A 35- to 37-kDa glycoprotein (gp35-37) is the polypeptide most frequently and intensively recognized by KS ...[more]

PMID: 9658120

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Project description:Herpesviruses alternate between the latent and the lytic life cycle. Switching into the lytic life cycle is important for herpesviral replication and disease pathogenesis. Activation of a transcription factor replication and transcription activator (RTA) has been demonstrated to govern this switch in Kaposi's sarcoma-associated herpesvirus (KSHV). The protein encoded by open reading frame 49 from KSHV (ORF49KSHV) has been shown to upregulate lytic replication in KSHV by enhancing the activities of the RTA. We have solved the crystal structure of the ORF49KSHV protein to a resolution of 2.4 Å. The ORF49KSHV protein has a novel fold consisting of 12 alpha-helices bundled into two pseudodomains. Most notably are distinct charged patches on the protein surface, which are possible protein-protein interaction sites. Homologs of the ORF49KSHV protein in the gammaherpesvirus subfamily have low sequence similarities. Conserved residues are mainly located in the hydrophobic regions, suggesting that they are more likely to play important structural roles than functional ones. Based on the identification and position of three sulfates binding to the positive areas, we performed some initial protein-DNA binding studies by analyzing the thermal stabilization of the protein in the presence of DNA. The ORF49KSHV protein is stabilized in a dose-responsive manner by double-stranded oligonucleotides, suggesting actual DNA interaction and binding. Biolayer interferometry studies also demonstrated that the ORF49KSHV protein binds these oligonucleotides. Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumorigenic gammaherpesvirus that causes multiple cancers and lymphoproliferative diseases. The virus exists mainly in the quiescent latent life cycle, but when it is reactivated into the lytic life cycle, new viruses are produced and disease symptoms usually manifest. Several KSHV proteins play important roles in this reactivation, but their exact roles are still largely unknown. In this study, we report the crystal structure of the open reading frame 49 protein encoded by KSHV (ORF49KSHV). Possible regions for protein interaction that could harbor functional importance were found on the surface of the ORF49KSHV protein. This led to the discovery of novel DNA binding properties of the ORF49KSHV protein. Evolutionary conserved structural elements with the functional homologs of ORF49KSHV were also established with the structure.

Project description:Human astrovirus (HAstV) strains exhibit high levels of genetic diversity, and many recombinant strains with different recombination patterns have been reported. The aims of the present study were to investigate the emergence of HAstV recombinant strains and to characterize the recombination patterns of the strains detected in pediatric patients admitted to the hospital with acute gastroenteritis in Chiang Mai, Thailand. A total of 92 archival HAstV strains detected in 2011 to 2020 were characterized regarding their open reading frame 1a (ORF1a) genotypes in comparison with their ORF1b genotypes to identify recombinant strains. The recombination breakpoints of the putative recombinant strains were determined by whole-genome sequencing and were analyzed by SimPlot and RDP software. Three HAstV strains (CMH-N178-12, CMH-S059-15, and CMH-S062-15) were found to be recombinant strains of three different HAstV genotypes, i.e., HAstV5, HAstV8, and HAstV1 within the ORF1a, ORF1b, and ORF2 regions, respectively. The CMH-N178-12 strain displayed recombination breakpoints at nucleotide positions 2681 and 4357 of ORF1a and ORF1b, respectively, whereas the other two recombinant strains, CMH-S059-15 and CMH-S062-15, displayed recombination breakpoints at nucleotide positions 2612 and 4357 of ORF1a and ORF1b, respectively. This is the first study to reveal nearly full-length genome sequences of HAstV recombinant strains with a novel recombination pattern of ORF1a-ORF1b-ORF2 genotypes. This finding may be useful as a guideline for identifying other recombinant HAstV strains in other geographical regions and may provide a better understanding of their genetic diversity, as well as basic knowledge regarding virus evolution. IMPORTANCE Recombination is one of the mechanisms that plays a crucial role in the genetic diversity and evolution of HAstV. We wished to investigate the emergence of HAstV recombinant strains and to analyze the whole-genome sequences of the putative HAstV recombinant strains detected in pediatric patients with acute gastroenteritis in 2011 to 2020. We reported 3 novel intergenotype recombinant strains of HAstV5-HAstV8-HAstV1 at the ORF1a-ORF1b-ORF2 regions of the HAstV genome. The hot spots of recombination occur frequently near the ORF1a-ORF1b and ORF1b-ORF2 junctions of the HAstV genome. The findings indicate that intergenotype recombination of HAstV occurs frequently in nature. The emergence of a novel recombinant strain allows the new virus to adapt and successfully escape from the host immune system, eventually emerging as the predominant genotype to infect human populations that lack herd immunity against novel recombinant strains. The virus may cause an outbreak and needs to be monitored continually.

Dataset Information

The immunogenic glycoprotein gp35-37 of human herpesvirus 8 is encoded by open reading frame K8.1.

Publications

The immunogenic glycoprotein gp35-37 of human herpesvirus 8 is encoded by open reading frame K8.1.

Similar Datasets

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