scholarly journals Small but mighty: Functional landscape of the versatile geminivirus-encoded C4 protein

2021 ◽  
Vol 17 (10) ◽  
pp. e1009915
Author(s):  
Laura Medina-Puche ◽  
Anelise F. Orílio ◽  
F. Murilo Zerbini ◽  
Rosa Lozano-Durán

The fast-paced evolution of viruses enables them to quickly adapt to the organisms they infect by constantly exploring the potential functional landscape of the proteins encoded in their genomes. Geminiviruses, DNA viruses infecting plants and causing devastating crop diseases worldwide, produce a limited number of multifunctional proteins that mediate the manipulation of the cellular environment to the virus’ advantage. Among the proteins produced by the members of this family, C4, the smallest one described to date, is emerging as a powerful viral effector with unexpected versatility. C4 is the only geminiviral protein consistently subjected to positive selection and displays a number of dynamic subcellular localizations, interacting partners, and functions, which can vary between viral species. In this review, we aim to summarize our current knowledge on this remarkable viral protein, encompassing the different aspects of its multilayered diversity, and discuss what it can teach us about geminivirus evolution, invasion requirements, and virulence strategies.

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1035
Author(s):  
Guohui Li ◽  
Xinyu Qi ◽  
Zhaoyang Hu ◽  
Qi Tang

Typical viral propagation involves sequential viral entry, uncoating, replication, gene transcription and protein synthesis, and virion assembly and release. Some viral proteins must be transported into host nucleus to facilitate viral propagation, which is essential for the production of mature virions. During the transport process, nuclear localization signals (NLSs) play an important role in guiding target proteins into nucleus through the nuclear pore. To date, some classical nuclear localization signals (cNLSs) and non-classical NLSs (ncNLSs) have been identified in a number of viral proteins. These proteins are involved in viral replication, expression regulation of viral genes and virion assembly. Moreover, other proteins are transported into nucleus with unknown mechanisms. This review highlights our current knowledge about the nuclear trafficking of cellular proteins associated with viral propagation.


2012 ◽  
Vol 40 (4) ◽  
pp. 826-830 ◽  
Author(s):  
Elaine A. Hong ◽  
Hannah L. Gautrey ◽  
David J. Elliott ◽  
Alison J. Tyson-Capper

SAFB1 (scaffold attachment factor B1) and a second family member SAFB2, are multifunctional proteins implicated in a variety of cellular processes including cell growth, apoptosis and stress response. Their potential function as tumour suppressors has been proposed based on well-described roles in tran-scriptional repression. The present review summarizes the current knowledge of SAFB1 and SAFB2 proteins in transcriptional repression with relevance to cancer.


2012 ◽  
Vol 302 (1) ◽  
pp. H24-H37 ◽  
Author(s):  
Elisabeth S. Christians ◽  
Ivor J. Benjamin

Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed “proteostasis.” Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e.g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e.g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans.


2021 ◽  
Author(s):  
Jing-Zhe Jiang ◽  
Yi-Fei Fang ◽  
Hong-Ying Wei ◽  
Ying-Xiang Guo ◽  
Li-Ling Yang ◽  
...  

Abstract Background:Viruses are the most abundant biological entities, and they play critical roles in entire ecosystems. Nevertheless, current knowledge about them is no more than 1% of the estimated diversity of the Earth’s virosphere. Oysters are filter-feeding molluscan bivalves and are ideal sentinels for marine virus exploration and viral ecology studies. Results: Here we report a Dataset of Oyster Virome (DOV) that contains 728,784 nonredundant viral operational taxonomic unit (vOTU) contigs and 3,473 high-quality viral genomes, enabling the first comprehensive overview of viral communities in oysters. As in other marine viromes, families Siphoviridae, Podoviridae, and Myoviridae are dominant in the DOV. However, Circoviridae is the most abundant family among the high-quality genomes, indicating that oysters may be their potential hotspots. Despite performing target amplification for RNA genomes, the diversity of RNA viruses was much lower than the diversity of DNA viruses. Notably, most of the vOTUs in the DOV were previously undescribed viruses and could not be clustered with any sequences in three reference datasets. Three approaches (based on references, vOTUs, and auxiliary metabolic genes) consistently showed that host health status, location, and sampling date had potential impacts on virome structures. Conclusions: This study highlights the practicality of oysters for marine virus exploration and provides a new direction to understand the relationship between marine bivalves and the environment.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2234
Author(s):  
Ena Pešut ◽  
Anamaria Đukić ◽  
Lucija Lulić ◽  
Josipa Skelin ◽  
Ivana Šimić ◽  
...  

Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and on-going research in Croatia.


2021 ◽  
Author(s):  
Anwesha Banerjee ◽  
Anupam Mukherjee

MicroRNAs (miRNAs), first discovered in the year 1993 in the nematode C. elegans, are small, approximately 22-nucleotide-long, non-coding RNAs that regulate gene expression. Cellular miRNAs have been implicated in the control of many biological processes, and their dysregulation is associated with different diseases. They can be significantly up/downregulated upon infection or disease, serving as excellent biomarkers and therapeutic targets. Several human DNA viruses, including many herpesviruses, have now been reported to encode viral miRNAs. There are a variety of possible interactions and mechanisms of viral microRNAs (vmiRNAs) which are yet to be remains obscure. Viral miRNAs can function as orthologs of cellular miRNAs and regulate their expression. Additionally, viruses have also developed vmiRNA mechanisms to avoid being targeted by the host miRNAs. Herpes Simplex Viruses (HSV-1 & HSV-2) cause genital and oral herpes, establishing lifelong latent infections in their hosts, and it is one of the most prevalent sexually transmitted infections (STIs) worldwide. vmiRNAs play essential roles in Herpesvirus biology. In this chapter, we will discuss the current knowledge about miRNAs and their role in different stages of Herpesvirus infection. It will also elaborate the biomarkers, therapeutic potential of these molecules, and the prospective areas of future research.


Author(s):  
Mila Collados Rodríguez

The constitutive expression of Speckled-100 (Sp100) is known to restrict the replication of many clinically important DNA viruses. This pre-existing (intrinsic) immune defense to virus infection can be further upregulated upon interferon (IFN) stimulation as a component of the innate immune response. In humans, Sp100 is encoded by a single gene locus, which can produce alternatively spliced isoforms. The widely studied Sp100A, Sp100B, Sp100C and Sp100HMG have functions associated with the transcriptional regulation of viral and cellular chromatin, either directly through their characteristic DNA-binding domains, or indirectly through post-translational modification (PTM) and associated protein interaction networks. Sp100 isoforms are resident component proteins of promyelocytic leukemia-nuclear bodies (PML-NBs), dynamic nuclear sub-structures which regulate host immune defenses against many pathogens. In the case of human herpesviruses, multiple protein antagonists are expressed to relieve viral DNA genome transcriptional silencing imposed by PML-NB and Sp100-derived proteinaceous structures, thereby stimulating viral propagation, pathogenesis, and transmission to new hosts. This review details how different Sp100 isoforms are manipulated during herpesviruses HSV1, VZV, HCMV, EBV, and KSHV infection, identifying gaps in our current knowledge, and highlighting future areas of research.


Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1313
Author(s):  
Diego Forni ◽  
Rachele Cagliani ◽  
Manuela Sironi

The Betacoronavirus genus of mammal-infecting viruses includes three subgenera (Sarbecovirus, Embecovirus, and Merbecovirus), in which most known human coronaviruses, including SARS-CoV-2, cluster. Coronaviruses are prone to host shifts, with recombination and positive selection possibly contributing to their high zoonotic potential. We analyzed the role of these two forces in the evolution of viruses belonging to the Betacoronavirus genus. The results showed that recombination has been pervasive during sarbecovirus evolution, and it is more widespread in this subgenus compared to the other two. In both sarbecoviruses and merbecoviruses, recombination hotspots are clearly observed. Conversely, positive selection was a less prominent force in sarbecoviruses compared to embecoviruses and merbecoviruses and targeted distinct genomic regions in the three subgenera, with S being the major target in sarbecoviruses alone. Overall, the results herein indicate that Betacoronavirus subgenera evolved along different trajectories, which might recapitulate their host preferences or reflect the origins of the presently available coronavirus sequences.


Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1034
Author(s):  
Sian Lant ◽  
Carlos Maluquer de Motes

The ubiquitin system has emerged as a master regulator of many, if not all, cellular functions. With its large repertoire of conjugating and ligating enzymes, the ubiquitin system holds a unique mechanism to provide selectivity and specificity in manipulating protein function. As intracellular parasites viruses have evolved to modulate the cellular environment to facilitate replication and subvert antiviral responses. Poxviruses are a large family of dsDNA viruses with large coding capacity that is used to synthetise proteins and enzymes needed for replication and morphogenesis as well as suppression of host responses. This review summarises our current knowledge on how poxvirus functions rely on the cellular ubiquitin system, and how poxviruses exploit this system to their own advantage, either facilitating uncoating and genome release and replication or rewiring ubiquitin ligases to downregulate critical antiviral factors. Whilst much remains to be known about the intricate interactions established between poxviruses and the host ubiquitin system, our knowledge has revealed crucial viral processes and important restriction factors that open novel avenues for antiviral treatment and provide fundamental insights on the biology of poxviruses and other virus families.


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