Alternative peptide-fusion proteins generated by out-of-frame mutations, just upstream ORFs or elongations in mutants of Human Hepatitis B Viruses

Faure, Éric

doi:10.1016/j.virusres.2005.10.023

Cited by 13 publications

(9 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are two principal types of overlap: (1) the same-strand type in which the two genes involved are transcribed from the same strand but in different reading frames and (2) the different-strand type in which the two genes are transcribed from different strands. Overlapping genes are known to be common in viruses, mitochondria, bacteria, plasmids and even in vertebrates (references in [50,51]). However, with the exception of viruses [52], it is widely assumed that only one strand can encode a protein and that the non-coding strands do not, although they can play a role in regulation [53].…”

Section: Discussionmentioning

confidence: 99%

Probable presence of an ubiquitous cryptic mitochondrial gene on the antisense strand of the cytochrome oxidase I gene

Faure

Delaye

Tribolo³

et al. 2011

Biol Direct

View full text Add to dashboard Cite

BackgroundMitochondria mediate most of the energy production that occurs in the majority of eukaryotic organisms. These subcellular organelles contain a genome that differs from the nuclear genome and is referred to as mitochondrial DNA (mtDNA). Despite a disparity in gene content, all mtDNAs encode at least two components of the mitochondrial electron transport chain, including cytochrome c oxidase I (Cox1).Presentation of the hypothesisA positionally conserved ORF has been found on the complementary strand of the cox1 genes of both eukaryotic mitochondria (protist, plant, fungal and animal) and alpha-proteobacteria. This putative gene has been named gau for gene antisense ubiquitous in mtDNAs. The length of the deduced protein is approximately 100 amino acids. In vertebrates, several stop codons have been found in the mt gau region, and potentially functional gau regions have been found in nuclear genomes. However, a recent bioinformatics study showed that several hypothetical overlapping mt genes could be predicted, including gau; this involves the possible import of the cytosolic AGR tRNA into the mitochondria and/or the expression of mt antisense tRNAs with anticodons recognizing AGR codons according to an alternative genetic code that is induced by the presence of suppressor tRNAs. Despite an evolutionary distance of at least 1.5 to 2.0 billion years, the deduced Gau proteins share some conserved amino acid signatures and structure, which suggests a possible conserved function. Moreover, BLAST analysis identified rare, sense-oriented ESTs with poly(A) tails that include the entire gau region. Immunohistochemical analyses using an anti-Gau monoclonal antibody revealed strict co-localization of Gau proteins and a mitochondrial marker.Testing the hypothesisThis hypothesis could be tested by purifying the gau gene product and determining its sequence. Cell biological experiments are needed to determine the physiological role of this protein.Implications of the hypothesisStudies of the gau ORF will shed light on the origin of novel genes and their functions in organelles and could also have medical implications for human diseases that are caused by mitochondrial dysfunction. Moreover, this strengthens evidence for mitochondrial genes coded according to an overlapping genetic code.

show abstract

Section: Discussionmentioning

confidence: 99%

Probable presence of an ubiquitous cryptic mitochondrial gene on the antisense strand of the cytochrome oxidase I gene

Faure

Delaye

Tribolo³

et al. 2011

Biol Direct

View full text Add to dashboard Cite

show abstract

“…The global prevalence of chronic hepatitis B virus (HBV) infection is estimated at 240 million infections, and these infections contribute to ∼600,000 deaths annually due to complications such as liver failure, cirrhosis, and hepatocellular carcinorma [Ott et al, ]. HBV is an enveloped, 3.2 kb partially double‐stranded DNA virus, which belongs to the Hepadnaviridae family [Faure, ]. Like retroviruses, HBV also uses a reverse transcriptase enzyme during replication, resulting in high HBV diversity [Olinger et al, ].…”

Section: Introductionmentioning

confidence: 99%

Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV

Mayaphi

Martin

Mphahlele

et al. 2013

Journal of Medical Virology

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for two which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g., P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5–7%. Several study sequences were highly divergent from other African subgeno-type A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAg-negative chronic hepatitis B responds poorly to conventional interferon-α therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBV-related diseases.

show abstract

“…In a subgroup of Theiler's murine encephalomyelitis virus, translation of an ARF produces a protein that appears to increase demyelinating activity (64) and may also play a role in cell tropism, thus restricting infection to cell populations that serve as reservoirs for the virus (65). Variations in the hepatitis B virus genome have revealed cryptic ORFs encoding long ARF sequences associated predominantly with patients demonstrating severe disease, suggesting a role of these sequences in viral pathogenesis (66).…”

Section: Impact Of Cryptic Epitopes On T Cell Selection and Immunitymentioning

confidence: 99%

Alternative Translational Products and Cryptic T Cell Epitopes: Expecting the Unexpected

Green

2006

The Journal of Immunology

View full text Add to dashboard Cite

Although CD8 T cell epitopes have been studied extensively, often overlooked are unconventional cryptic epitopes generated from nontraditional sources of peptides/proteins and/or mechanisms of translation. In this review, we discuss alternative reading frame epitopes, both mechanistically and also in terms of their physiologic importance in the induction of antiviral and antitumor CTL responses. Issues of the influence of cryptic translational products on foreign and self-Ag diversity, thymic selection, and the T cell repertoire; disease pathogenesis; and approaches to vaccine design are discussed in context of the potentially large impact of unconventional epitopes on T cell immunity.

show abstract

Alternative peptide-fusion proteins generated by out-of-frame mutations, just upstream ORFs or elongations in mutants of Human Hepatitis B Viruses

Cited by 13 publications

References 87 publications

Probable presence of an ubiquitous cryptic mitochondrial gene on the antisense strand of the cytochrome oxidase I gene

Probable presence of an ubiquitous cryptic mitochondrial gene on the antisense strand of the cytochrome oxidase I gene

Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV

Alternative Translational Products and Cryptic T Cell Epitopes: Expecting the Unexpected

Contact Info

Product

Resources

About