The Multifaceted Oncoprotein Tax

Kfoury, Youmna; Nasr, Rihab; Journo, Chloé; Mahieux, Renaud; Pique, Claudine; Bazarbachi, Ali

doi:10.1016/b978-0-12-394280-7.00003-8

Cited by 39 publications

(28 citation statements)

References 231 publications

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“…In the alphanodavirus replicase/B2 overlap (case study 2), several elements suggest that horizontal transfer might have taken place and thus that the codon usage prediction is not reliable. In the deltaretrovirus Tax/Rex overlap (case study 1), our prediction that Rex has originated de novo by overprinting Tax is consistent with the function of Tax, which occurs upstream of that of Rex in the viral cycle [37], [39], [54]. It is also coherent with the fact that Tax has a higher sequence complexity than Rex or p30, and is under stronger selection pressure than Rex [55], [56], which is generally the case of ancestral frames [3], [4].…”

Section: Discussionmentioning

confidence: 57%

“…Both Tax and Rex are present in all deltaretroviruses and only in those viruses, which suggests that Tax originated first in the common ancestor of deltaretroviruses , and that Rex originated by overprinting it “rapidly” afterwards (by biological timescales), before the divergence of deltaretroviruses . Rex must have then undergone a rapid functionalization, since it is indispensable for the viral cycle, like Tax [37], [39], [54].…”

Section: Discussionmentioning

confidence: 99%

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Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses

2013

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A well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes, e.g. by duplication or horizontal transfer. In contrast, many viruses generate protein-coding genes de novo, via the overprinting of a new reading frame onto an existing (“ancestral”) frame. This mechanism is thought to play an important role in viral pathogenicity, but has been poorly explored, perhaps because identifying the de novo frames is very challenging. Therefore, a new approach to detect them was needed. We assembled a reference set of overlapping genes for which we could reliably determine the ancestral frames, and found that their codon usage was significantly closer to that of the rest of the viral genome than the codon usage of de novo frames. Based on this observation, we designed a method that allowed the identification of de novo frames based on their codon usage with a very good specificity, but intermediate sensitivity. Using our method, we predicted that the Rex gene of deltaretroviruses has originated de novo by overprinting the Tax gene. Intriguingly, several genes in the same genomic region have also originated de novo and encode proteins that regulate the functions of Tax. Such “gene nurseries” may be common in viral genomes. Finally, our results confirm that the genomic GC content is not the only determinant of codon usage in viruses and suggest that a constraint linked to translation must influence codon usage.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses

2013

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“…Post-translational modifications of Tax-1 and Tax-2 such as phosphorylation, acetylation, ubiquitination, and sumoylation have been extensively described in recent reviews (Bertazzoni et al, 2011; Lodewick et al, 2011; Kfoury et al, 2012). Recent comparative analyses of Tax-1 and Tax-2 post-translational modifications centered on the contribution of ubiquitination and sumoylation to the intracellular localization of Tax and its ability to activate NF-κB (Lamsoul et al, 2005; Kfoury et al, 2006; Nasr et al, 2006; Turci et al, 2009, 2012; Bonnet et al, 2012; Xiao, 2012; Zane and Jeang, 2012; Journo et al, 2013).…”

Section: Comparison Of Tax Proteins Structuresmentioning

confidence: 99%

Highlights on distinctive structural and functional properties of HTLV Tax proteins

Romanelli¹,

Diani²,

Bergamo³

et al. 2013

Front. Microbiol.

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Human T cell leukemia viruses (HTLVs) are complex human retroviruses of the Deltaretrovirus genus. Four types have been identified thus far, with HTLV-1 and HTLV-2 much more prevalent than HTLV-3 or HTLV-4. HTLV-1 and HTLV-2 possess strictly related genomic structures, but differ significantly in pathogenicity, as HTLV-1 is the causative agent of adult T cell leukemia and of HTLV-associated myelopathy/tropical spastic paraparesis, whereas HTLV-2 is not associated with neoplasia. HTLVs code for a protein named Tax that is responsible for enhancing viral expression and drives cell transformation. Much effort has been invested to dissect the impact of Tax on signal transduction pathways and to identify functional differences between the HTLV Tax proteins that may explain the distinct oncogenic potential of HTLV-1 and HTLV-2. This review summarizes our current knowledge of Tax-1 and Tax-2 with emphasis on their structure, role in activation of the NF-κB (nuclear factor kappa-B) pathway, and interactions with host factors.

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“…The precise subcellular localization where these events occur and their molecular requirements remain largely unknown. We and others recently demonstrated that NF-κB activation is dependent on Tax post-translational modifications, namely ubiquitylation and sumoylation (Lamsoul et al, 2005; Nasr et al, 2006; Kfoury et al, 2008, 2011, 2012), which result in the activation of the IKK complex, phosphorylation of the NF-κB inhibitor IκB, ultimately resulting in the nuclear translocation of the active NF-κB subunits and activation of NF-κB-dependent genes (reviewed in Kfoury et al, 2005, 2012). In addition, Peloponese et al (2004) reported that ubiquitin addition modifies Tax in a proteasome-independent manner from an active to a less-active transcriptional form.…”

Section: Transgenic Mice Models Of Htlv-1mentioning

confidence: 99%

Animal models on HTLV-1 and related viruses: what did we learn?

et al. 2012

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Retroviruses are associated with a wide variety of diseases, including immunological, neurological disorders, and different forms of cancer. Among retroviruses, Oncovirinae regroup according to their genetic structure and sequence, several related viruses such as human T-cell lymphotropic viruses types 1 and 2 (HTLV-1 and HTLV-2), simian T cell lymphotropic viruses types 1 and 2 (STLV-1 and STLV-2), and bovine leukemia virus (BLV). As in many diseases, animal models provide a useful tool for the studies of pathogenesis, treatment, and prevention. In the current review, an overview on different animal models used in the study of these viruses will be provided. A specific attention will be given to the HTLV-1 virus which is the causative agent of adult T-cell leukemia/lymphoma (ATL) but also of a number of inflammatory diseases regrouping the HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), infective dermatitis and some lung inflammatory diseases. Among these models, rabbits, monkeys but also rats provide an excellent in vivo tool for early HTLV-1 viral infection and transmission as well as the induced host immune response against the virus. But ideally, mice remain the most efficient method of studying human afflictions. Genetically altered mice including both transgenic and knockout mice, offer important models to test the role of specific viral and host genes in the development of HTLV-1-associated leukemia. The development of different strains of immunodeficient mice strains (SCID, NOD, and NOG SCID mice) provide a useful and rapid tool of humanized and xenografted mice models, to test new drugs and targeted therapy against HTLV-1-associated leukemia, to identify leukemia stem cells candidates but also to study the innate immunity mediated by the virus. All together, these animal models have revolutionized the biology of retroviruses, their manipulation of host genes and more importantly the potential ways to either prevent their infection or to treat their associated diseases.

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The Multifaceted Oncoprotein Tax

Cited by 39 publications

References 231 publications

Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses

Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses

Highlights on distinctive structural and functional properties of HTLV Tax proteins

Animal models on HTLV-1 and related viruses: what did we learn?

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