The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions

Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis. Flavivirus infections underlie multiple human diseases and thus exert an immense burden on public health worldwide. Mounting evidence indicates that host autophagy is subverted to modulate the life cycles of flaviviruses, such as hepatitis C virus, dengue virus, Japanese encephalitis virus, West Nile virus and Zika virus. The diverse interplay between autophagy and flavivirus infection not only regulates viral growth in host cells but also counteracts host stress responses induced by viral infection. In this review, we summarize the current knowledge on the role of autophagy in the flavivirus life cycle. We also discuss the impacts of virus-induced autophagy on the pathogeneses of flavivirus-associated diseases and the potential use of autophagy as a therapeutic target for curing flavivirus infections and related human diseases.

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T6SS Mediated Stress Responses for Bacterial Environmental Survival and Host Adaptation

International Journal of Molecular Sciences ◽

10.3390/ijms22020478 ◽

2021 ◽

Vol 22 (2) ◽

pp. 478

Author(s):

Kai-Wei Yu ◽

Peng Xue ◽

Yang Fu ◽

Liang Yang

Keyword(s):

Protein Secretion ◽

Stress Responses ◽

Current Knowledge ◽

Bacterial Species ◽

Host Cells ◽

Interspecies Interactions ◽

Type Vi Secretion System ◽

Membrane Complex ◽

Type Vi Secretion ◽

Bacterial Type

The bacterial type VI secretion system (T6SS) is a protein secretion apparatus widely distributed in Gram-negative bacterial species. Many bacterial pathogens employ T6SS to compete with the host and to coordinate the invasion process. The T6SS apparatus consists of a membrane complex and an inner tail tube-like structure that is surrounded by a contractile sheath and capped with a spike complex. A series of antibacterial or antieukaryotic effectors is delivered by the puncturing device consisting of a Hcp tube decorated by the VgrG/PAAR complex into the target following the contraction of the TssB/C sheath, which often leads to damage and death of the competitor and/or host cells. As a tool for protein secretion and interspecies interactions, T6SS can be triggered by many different mechanisms to respond to various physiological conditions. This review summarizes our current knowledge of T6SS in coordinating bacterial stress responses against the unfavorable environmental and host conditions.

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Mechanisms of Giardia lamblia differentiation into cysts

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.61.3.294-304.1997 ◽

1997 ◽

Vol 61 (3) ◽

pp. 294-304

Author(s):

H D Luján ◽

M R Mowatt ◽

T E Nash

Keyword(s):

Giardia Lamblia ◽

Current Knowledge ◽

Regulation Of Gene Expression ◽

Life Cycles ◽

Eukaryotic Cells ◽

Organelle Biogenesis ◽

Adaptive Responses ◽

Specific Stimulus ◽

Adverse Conditions

Microbiologists have long been intrigued by the ability of parasitic organisms to adapt to changes in the environment. Since most parasites occupy several niches during their journey between vectors and hosts, they have developed adaptive responses which allow them to survive under adverse conditions. Therefore, the life cycles of protozoan and helminthic parasites are excellent models with which to study numerous mechanisms involved in cell differentiation, such as the regulation of gene expression, signal transduction pathways, and organelle biogenesis. Unfortunately, many of these studies are very difficult because the conditions needed to elicit developmental changes in parasites remain undetermined in most cases. Recently, several interesting findings were reported on the process of differentiation of Giardia lamblia trophozoites into cysts. G. lamblia is a flagellated protozoan that inhabits the upper small intestine of its vertebrate host and is a major cause of enteric disease worldwide. It belongs to the earliest identified lineage among eukaryotes and therefore offers a unique insight into the progression from primitive to more complex eukaryotic cells. The discovery of a specific stimulus that induces trophozoites to differentiate into cysts, the identification and characterization of encystation-specific molecules, the elucidation of novel biochemical pathways, and the development of useful reagents and techniques have made this parasite an excellent model with which to study differentiation in eukaryotic cells. In this review, we summarize the most recent fundings on several aspects of Giardia differentiation and discuss the significance of these findings within the context of current knowledge in the field.

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Epigenetic Lens to Visualize the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection in COVID-19 Pandemic

Frontiers in Genetics ◽

10.3389/fgene.2021.581726 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nitin Saksena ◽

Srinivasa Reddy Bonam ◽

Monica Miranda-Saksena

Keyword(s):

Immune Response ◽

Current Knowledge ◽

Rna Virus ◽

Expression Patterns ◽

Host Cells ◽

Human Populations ◽

Host Interactions ◽

Epigenetic Machinery ◽

Immune Sensing ◽

Post Entry

In <20 years, we have witnessed three different epidemics with coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2 in human populations, causing widespread mortality. SARS-CoV-2, through its rapid global spread, has led to the pandemic that we call COVID-19. As of February 1, 2021, the global infections linked to SARS-CoV-2 stand at 103,503,340, with 2,236,960 deaths, and 75,108,099 recoveries. This review attempts to highlight host-pathogen interaction with particular emphasis on the role of epigenetic machinery in regulating the disease. Although researchers, since the start of the pandemic, have been intensely engaged in diverse areas to understand the mechanisms involved in SARS-CoV-2 infection to find answers that can bring about innovative ways to swiftly treat and prevent disease progression, this review provides an overview on how the host epigenetics is modulated and subverted by SARS-CoV-2 to enter the host cells and drive immunopathogenesis. Epigenetics is the study that combines genetic and non-genetic factors controlling phenotypic variation, which are primarily a consequence of external and environmental stimuli. These stimuli alter the activity of a gene without impinging on the DNA code. In viral-host interactions, DNA/RNA methylation, non-coding RNAs, chromatin remodeling, and histone modifications are known to regulate and modulate host gene expression patterns. Viruses such as Coronaviruses (an RNA virus) show intrinsic association with these processes. They have evolved the ability to tamper with host epigenetic machinery to interfere with immune sensing pathways to evade host immune response, thereby enhancing its replication and pathogenesis post-entry. These epigenetic alterations allow the virus to weaken the host's immune response to successfully spread infection. How this occurs, and what epigenetic mechanisms are altered is poorly understood both for coronaviruses and other respiratory RNA viruses. The review highlights several cutting-edge aspects of epigenetic work primarily pertinent to SARS-CoV-2, which has been published between 2019 and 2020 to showcase the current knowledge both in terms of success and failures and take lessons that will assist us in understanding the disease to develop better treatments suited to kill SARS-CoV-2.

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Remedying the Mitochondria to Cure Human Diseases by Natural Products

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5232614 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Jian-Kang Mu ◽

Yan-Qin Li ◽

Ting-Ting Shi ◽

Li-Ping Yu ◽

Ya-Qin Yang ◽

...

Keyword(s):

Natural Products ◽

Mitochondrial Dysfunction ◽

Mechanism Of Action ◽

Current Knowledge ◽

Human Diseases ◽

Mitochondrial Regulation ◽

The Relationship

Mitochondria are the ‘engine’ of cells. Mitochondrial dysfunction is an important mechanism in many human diseases. Many natural products could remedy the mitochondria to alleviate mitochondria-involved diseases. In this review, we summarized the current knowledge of the relationship between the mitochondria and human diseases and the regulation of natural products to the mitochondria. We proposed that the development of mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represents an attractive strategy for a mitochondria-involved disorder therapy. Moreover, investigating the mitochondrial regulation of natural products can potentiate the in-depth comprehension of the mechanism of action of natural products.

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IKKε isoform switching governs the immune response against EV71 infection

Communications Biology ◽

10.1038/s42003-021-02187-x ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Ya-Ling Chang ◽

Yu-Wen Liao ◽

Min-Hsuan Chen ◽

Sui-Yuan Chang ◽

Yao-Ting Huang ◽

...

Keyword(s):

Host Cells ◽

Ev71 Infection ◽

Virus Propagation ◽

Host Interactions ◽

Reciprocal Interactions ◽

Isoform Switching ◽

Gene Regulatory ◽

Potential Strategy ◽

Antiviral Innate Immunity ◽

Interferon Responses

AbstractThe reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.

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Foamy Viruses, Bet, and APOBEC3 Restriction

Viruses ◽

10.3390/v13030504 ◽

2021 ◽

Vol 13 (3) ◽

pp. 504

Author(s):

Ananda Ayyappan Jaguva Vasudevan ◽

Daniel Becker ◽

Tom Luedde ◽

Holger Gohlke ◽

Carsten Münk

Keyword(s):

Current Knowledge ◽

Regulatory Protein ◽

Host Population ◽

Life Cycles ◽

Restriction Factors ◽

Host Restriction ◽

Open Questions ◽

Foamy Viruses ◽

Natural Hosts ◽

Hiv 1

Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV–host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.

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Evolution, expression and functional analysis of cultivated allotetraploid cotton DIR genes

BMC Plant Biology ◽

10.1186/s12870-021-02859-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhengwen Liu ◽

Xingfen Wang ◽

Zhengwen Sun ◽

Yan Zhang ◽

Chengsheng Meng ◽

...

Keyword(s):

Gene Family ◽

Stress Responses ◽

Rapid Evolution ◽

Gene Clusters ◽

Vital Role ◽

Fiber Development ◽

Rna Seq ◽

Evolutionarily Conserved ◽

Cell Wall Development ◽

Tandem Duplications

Abstract Background Dirigent (DIR) proteins mediate regioselectivity and stereoselectivity during lignan biosynthesis and are also involved in lignin, gossypol and pterocarpan biosynthesis. This gene family plays a vital role in enhancing stress resistance and in secondary cell-wall development, but systematical understanding is lacking in cotton. Results In this study, 107 GbDIRs and 107 GhDIRs were identified in Gossypium barbadense and Gossypium hirsutum, respectively. Most of these genes have a classical gene structure without intron and encode proteins containing a signal peptide. Phylogenetic analysis showed that cotton DIR genes were classified into four distinct subfamilies (a, b/d, e, and f). Of these groups, DIR-a and DIR-e were evolutionarily conserved, and segmental and tandem duplications contributed equally to their formation. In contrast, DIR-b/d mainly expanded by recent tandem duplications, accompanying with a number of gene clusters. With the rapid evolution, DIR-b/d-III was a Gossypium-specific clade involved in atropselective synthesis of gossypol. RNA-seq data highlighted GhDIRs in response to Verticillium dahliae infection and suggested that DIR gene family could confer Verticillium wilt resistance. We also identified candidate DIR genes related to fiber development in G. barbadense and G. hirsutum and revealed their differential expression. To further determine the involvement of DIR genes in fiber development, we overexpressed a fiber length-related gene GbDIR78 in Arabidopsis and validated its function in trichomes and hypocotyls. Conclusions These findings contribute novel insights towards the evolution of DIR gene family and provide valuable information for further understanding the roles of DIR genes in cotton fiber development as well as in stress responses.

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Lankesterella (Apicomplexa, Lankesterellidae) Blood Parasites of Passeriform Birds: Prevalence, Molecular and Morphological Characterization, with Notes on Sporozoite Persistence In Vivo and Development In Vitro

Animals ◽

10.3390/ani11051451 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1451

Author(s):

Carolina Romeiro Fernandes Chagas ◽

Josef Harl ◽

Vytautas Preikša ◽

Dovilė Bukauskaitė ◽

Mikas Ilgūnas ◽

...

Keyword(s):

Morphological Characterization ◽

Life Cycles ◽

Diagnostic Methods ◽

Host Cells ◽

Blood Parasites ◽

Serinus Canaria ◽

Long Time ◽

Development In Vitro

Recent studies confirmed that some Hepatozoon-like blood parasites (Apicomplexa) of birds are closely related to the amphibian parasite Lankesterella minima. Little is known about the biology of these pathogens in birds, including their distribution, life cycles, specificity, vectors, and molecular characterization. Using blood samples of 641 birds from 16 species, we (i) determined the prevalence and molecular diversity of Lankesterella parasites in naturally infected birds; (ii) investigated the development of Lankesterella kabeeni in laboratory-reared mosquitoes, Culex pipiens forma molestus and Aedes aegypti; and (iii) tested experimentally the susceptibility of domestic canaries, Serinus canaria, to this parasite. This study combined molecular and morphological diagnostic methods and determined 11% prevalence of Lankesterella parasites in Acrocephalidae birds; 16 Lankesterella lineages with a certain degree of host specificity and two new species (Lankesterella vacuolata n. sp. and Lankesterella macrovacuolata n. sp.) were found and characterized. Lankesterella kabeeni (formerly Hepatozoon kabeeni) was re-described. Serinus canaria were resistant after various experimental exposures. Lankesterella sporozoites rapidly escaped from host cells in vitro. Sporozoites persisted for a long time in infected mosquitoes (up to 42 days post exposure). Our study demonstrated a high diversity of Lankesterella parasites in birds, and showed that several avian Hepatozoon-like parasites, in fact, belong to Lankesterella genus.

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Humanizing the yeast origin recognition complex

Nature Communications ◽

10.1038/s41467-020-20277-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Clare S. K. Lee ◽

Ming Fung Cheung ◽

Jinsen Li ◽

Yongqian Zhao ◽

Wai Hei Lam ◽

...

Keyword(s):

Amino Acid ◽

Protein Complex ◽

Origin Recognition Complex ◽

Specific Binding ◽

Life Cycles ◽

Amino Acid Insertion ◽

Evolutionarily Conserved ◽

Transcriptional Start Sites ◽

Eukaryote Genome ◽

Origin Recognition

AbstractThe Origin Recognition Complex (ORC) is an evolutionarily conserved six-subunit protein complex that binds specific sites at many locations to coordinately replicate the entire eukaryote genome. Though highly conserved in structure, ORC’s selectivity for replication origins has diverged tremendously between yeasts and humans to adapt to vastly different life cycles. In this work, we demonstrate that the selectivity determinant of ORC for DNA binding lies in a 19-amino acid insertion helix in the Orc4 subunit, which is present in yeast but absent in human. Removal of this motif from Orc4 transforms the yeast ORC, which selects origins based on base-specific binding at defined locations, into one whose selectivity is dictated by chromatin landscape and afforded with plasticity, as reported for human. Notably, the altered yeast ORC has acquired an affinity for regions near transcriptional start sites (TSSs), which the human ORC also favors.

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Research on Plants for the Understanding of Diseases of Nuclear and Mitochondrial Origin

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/836196 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Claudia P. Spampinato ◽

Diego F. Gomez-Casati

Keyword(s):

Current Knowledge ◽

Model System ◽

Human Diseases ◽

Model Organisms ◽

Human Cell Lines ◽

Molecular Defects ◽

Human Genes ◽

Clinical Disorders ◽

Mitochondrial Origin ◽

Experimental Findings

Different model organisms, such asEscherichia coli,Saccharomyces cerevisiae,Caenorhabditis elegans,Drosophila melanogaster, mouse, cultured human cell lines, among others, were used to study the mechanisms of several human diseases. Since human genes and proteins have been structurally and functionally conserved in plant organisms, the use of plants, especiallyArabidopsis thaliana, as a model system to relate molecular defects to clinical disorders has recently increased. Here, we briefly review our current knowledge of human diseases of nuclear and mitochondrial origin and summarize the experimental findings of plant homologs implicated in each process.

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