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Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding.

ABSTRACT: Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are human DNA tumor viruses that express nuclear antigens [latency-associated nuclear antigen 1 (LANA1) and Epstein-Barr nuclear antigen 1 (EBNA1)] necessary to maintain and replicate the viral genome. We report here that both LANA1 and EBNA1 undergo highly efficient +1/-2 programmed ribosomal frameshifting to generate previously undescribed alternative reading frame (ARF) proteins in their repeat regions. EBNA1(ARF) encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whereas KSHV LANA1(ARF) encodes a serine/arginine-like protein. Repeat sequence recoding has not been described previously for human DNA viruses. Programmed frameshifting (recoding) to generate multiple proteins from one RNA sequence can increase the coding capacity of a virus, without incurring a selective penalty against increased capsid size. The presence of similar repeat sequences in cellular genes, such as huntingtin, suggests that a comparison of repeat recoding in virus and human systems may provide functional and mechanistic insights for both systems.

SUBMITTER: Kwun HJ

PROVIDER: S-EPMC4205619 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding.

Kwun Hyun Jin HJ Toptan Tuna T Ramos da Silva Suzane S Atkins John F JF Moore Patrick S PS Chang Yuan Y

Proceedings of the National Academy of Sciences of the United States of America 20140930 41

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are human DNA tumor viruses that express nuclear antigens [latency-associated nuclear antigen 1 (LANA1) and Epstein-Barr nuclear antigen 1 (EBNA1)] necessary to maintain and replicate the viral genome. We report here that both LANA1 and EBNA1 undergo highly efficient +1/-2 programmed ribosomal frameshifting to generate previously undescribed alternative reading frame (ARF) proteins in their repeat regions. EBNA1(ARF) enc ...[more]

PMID: 25271323

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Project description:BackgroundHepatitis E virus (HEV) is a member of the family Hepeviridae and causes acute HEV infections resulting in thousands of deaths worldwide. The zoonotic nature of HEV in addition to its tendency from human to human transmission has led scientists across the globe to work on its different aspects. HEV also accounts for about 30% mortality rates in case of pregnant women. The genome of HEV is organized into three open reading frames (ORFs): ORF1 ORF2 and ORF3. A reading frame encoded protein ORF4 has recently been discovered which is exclusive to GT 1 isolates of HEV. The ORF4 is suggested to play crucial role in pregnancy-associated pathology and enhanced replication. Though studies have documented the ORF4's importance, the genetic features of ORF4 protein genes in terms of compositional patterns have not been elucidated. As codon usage performs critical role in establishment of the host-pathogen relationship, therefore, the present study reports the codon usage analysis (based on nucleotide sequences of HEV ORF4 available in the public database) in three hosts along with the factors influencing the codon usage patterns of the protein genes of ORF4 of HEV.ResultsThe nucleotide composition analysis indicated that ORF4 protein genes showed overrepresentation of C nucleotide and while A nucleotide was the least-represented, with random distribution of G and T(U) nucleotides. The relative synonymous codon usage (RSCU) analysis revealed biasness toward C/G-ended codons (over U/A) in all three natural HEV-hosts (human, rat and ferret). It was observed that all the ORF4 genes were richly endowed with GC content. Further, our results showed the occurrence of both coincidence and antagonistic codon usage patterns among HEV-hosts. The findings further emphasized that both mutational and selection forces influenced the codon usage patterns of ORF4 protein genes.ConclusionsTo the best of our knowledge, this is first bioinformatics study evaluating codon usage patterns in HEV ORF4 protein genes. The findings from this study are expected to increase our understanding toward significant factors involved in evolutionary changes of ORF4.Supplementary informationThe online version contains supplementary material available at 10.1186/s43088-022-00244-w.

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Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding.

Publications

Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding.

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