Host Stress Research Articles

Introgression and gene family contraction drive the evolution of lifestyle and host shifts of hypocrealean fungi

ABSTRACTHypocrealean fungi (Ascomycota) are known for their diversity of lifestyles. Their vital influences on agricultural and natural ecosystems have resulted in a number of sequenced genomes, which provide essential data for genomic analysis. Totally, 45 hypocrealean fungal genomes constructed a phylogeny. The phylogeny showed that plant pathogens in Nectriaceae diverged earliest, followed by animal pathogens in Cordycipitaceae, Ophiocordycipitaceae and Clavicipitaceae with mycoparasites in Hypocreaceae. Insect/nematode pathogens and grass endophytes in Clavicipitaceae diverged at last. Gene families associated with host-derived nutrients are significantly contracted in diverged lineages compared with the ancestral species. Introgression was detected in certain lineages of hypocrealean fungi, and the main functions of the genes located in the introgressed regions are involved in host recognition, transcriptional regulation, stress response and cell growth regulation. These results indicate that contraction of gene families and introgression might be main mechanisms to drive lifestyle differentiation and evolution and host shift of hypocrealean fungi.

Host heme oxygenase-1: Friend or foe in tackling pathogens?

Infectious diseases are a major challenge in management of human health worldwide. Recent literature suggests that host immune system could be modulated to ameliorate the pathogenesis of infectious disease. Heme oxygenase (HMOX1) is a key regulator of cellular signaling and it could be modulated using pharmacological reagents. HMOX1 is a cytoprotective enzyme that degrades heme to generate carbon monoxide (CO), biliverdin, and molecular iron. CO and biliverdin (or bilirubin derived from it) can restrict the growth of a few pathogens. Both of these also induce antioxidant pathways and anti-inflammatory pathways. On the other hand, molecular iron can induce proinflammatory pathway besides making the cellular environment oxidative in nature. Since microbial infections often induce oxidative stress in host cells/tissues, role of HMOX1 has been analyzed in the pathogenesis of number of infections. In this review, we have described the role of HMOX1 in pathogenesis of bacterial infections caused by Mycobacterium species, Salmonella and in microbial sepsis. We have also provided a succinct overview of the role of HMOX1 in parasitic infections such as malaria and leishmaniasis. In the end, we have also elaborated the role of HMOX1 in viral infections such as AIDS, hepatitis, dengue, and influenza. © 2018 IUBMB Life, 70(9):869-880, 2018.

OP-29 - Peroxidase, holdase and signaling functions of Trypanosoma cruzi mitochondrial peroxiredoxin

The etiological agent of Chagas disease, Trypanosoma cruzi contains 2-Cys peroxiredoxins (Prx) localized in mitochondria (TcMPX) and cytosol (TcCPX) as part of its antioxidant armamentarium. The participation of these Prx in the defense towards the host and parasite-derived oxidative stress led us to postulate them as virulence factors. In addition to its peroxidase activity, 2-Cys Prx have alternative functions. In this work, we studied the peroxidase, holdase and signaling functions of TcMPX in the context of parasite-macrophage and drug interactions (nifurtimox, NFX). Parasites overexpressing TcMPX were more infective compared to wild type (wt) under macrophage-derived O2•- and/or ONOO- generation indicating the protective role of TcMPX during infection. Additionally, TcMPX overexpressers also contain higher holdase activity and were more resistant to NFX-treatment. Importantly, wt parasites treated with NFX increase TcMPX protein content suggesting the involvement of the holdase activity in the stress response towards NFX. Finally, under stress conditions, TcMPX protein-disulfide adducts were detected indicating additional redox protein partners which may participate in the biological actions of TcMPX.

Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model.

Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort. CF-1 mice underwent alternating days of restraint and forced swim for 19 days (male n = 8, female n = 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated. Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p = .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected. These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.

Periodontal Disease and COPD

Periodontal disease is an inflammatory disease caused predominantly by Gram-negative, anaerobic, and microaerophilic bacteria that colonise the subgingival area though modified by environment, physical, social and host stresses. It results in progressive destruction of the periodontal ligament and alveolar bone with increased probing depth, recession, or both [1]. Throughout the history of mankind, it has been believed that oral diseases and maladies including periodontal disease may have an effect on the rest of the body. Over the centuries, writings from the ancient Egyptians, Hebrews, Assyrians, Greeks and Romans, have all noted the importance of the mouth in overall health and well-being. Thus, the concept of linking periodontitis and systemic diseases could be traced back to the beginning of recorded history and medicine [2]. Periodontal disease has been linked to an increased risk of various systemic diseases, including the respiratory diseases e.g. pneumonia and chronic obstructive pulmonary disease (COPD) [3]. COPD is a generic term defined by the presence of airflow obstruction with excess production of sputum resulting from chronic bronchitis and/or emphysema. It has been recognized as one of the major causes of death and disability globally and is the fourth leading cause of death in United States [4]. The aetiology of COPD is complex and multifactorial, involving multiple genetic and environmental factors [5]. An enhanced or abnormal inflammatory response to inhaled particles or gases, beyond the normal protective inflammatory response in the lungs, is a characteristic feature of COPD and is potential to produce lung injury

Impact of Three Different Mutations in Ehrlichia chaffeensis in Altering the Global Gene Expression Patterns

The rickettsial pathogen Ehrlichia chaffeensis causes a tick-borne disease, human monocytic ehrlichiosis. Mutations within certain genomic locations of the pathogen aid in understanding the pathogenesis and in developing attenuated vaccines. Our previous studies demonstrated that mutations in different genomic sites in E. chaffeensis caused variable impacts on their growth and attenuation in vertebrate and tick hosts. Here, we assessed the effect of three mutations on transcriptional changes using RNA deep-sequencing technology. RNA sequencing aided in detecting 66–80% of the transcripts of wildtype and mutant E. chaffeensis. Mutation in an antiporter gene (ECH_0379) causing attenuated growth in vertebrate hosts resulted in the down regulation of many transcribed genes. Similarly, a mutation downstream to the ECH_0490 coding sequence resulted in minimal impact on the pathogen’s in vivo growth, but caused major changes in its transcriptome. This mutation caused enhanced expression of several host stress response genes. Even though the ECH_0660 gene mutation caused the pathogen’s rapid clearance in vertebrate hosts and aids in generating a protective response, there was minimal impact on the transcriptome. The transcriptomic data offer novel insights about the impact of mutations on global gene expression and how they may contribute to the pathogen’s resistance and/or clearance from the host.

Gap analysis of Mycoplasma bovis disease, diagnosis and control: An aid to identify future development requirements.

There is a worldwide problem of disease caused by Mycoplasma (M.) bovis in cattle; it has a significant detrimental economic and animal welfare impact on cattle rearing. Infection can manifest as a plethora of clinical signs including mastitis, pneumonia, arthritis, keratoconjunctivitis, otitis media and genital disorders that may result in infertility and abortion. Current diagnosis and control information are reviewed and analysed to identify gaps in knowledge of the causative organism in respect of the disease pathology, diagnosis and control methods. The main considerations are as follows: no vaccines are commercially available; antimicrobial resistance is increasing; diagnostic and antimicrobial sensitivity testing needs to be improved; and a pen-side test would facilitate more rapid diagnosis and implementation of treatment with antimicrobials. More data on host susceptibility, stress factors, immune response and infectious dose levels are required. The impact of asymptomatic carriers, M.bovis survival in the environment and the role of wildlife in transmitting the disease also needs investigation. To facilitate development of vaccines, further analysis of more M.bovis genomes, its pathogenic mechanisms, including variable surface proteins, is required, along with reproducible disease models.

Confined Flow: Consequences and Implications for Bacteria and Biofilms.

Bacteria overwhelmingly live in geometrically confined habitats that feature small pores or cavities, narrow channels, or nearby interfaces. Fluid flows through these confined habitats are ubiquitous in both natural and artificial environments colonized by bacteria. Moreover, these flows occur on time and length scales comparable to those associated with motility of bacteria and with the formation and growth of biofilms, which are surface-associated communities that house the vast majority of bacteria to protect them from host and environmental stresses. This review describes the emerging understanding of how flow near surfaces and within channels and pores alters physical processes that control how bacteria disperse, attach to surfaces, and form biofilms. This understanding will inform the development and deployment of technologies for drug delivery, water treatment, and antifouling coatings and guide the structuring of bacterial consortia for production of chemicals and pharmaceuticals.

Transcriptome analysis provides insights into the delayed sticky disease symptoms in Carica papaya.

Global gene expression analysis indicates host stress responses, mainly those mediated by SA, associated to the tolerance to sticky disease symptoms at pre-flowering stage in Carica papaya. Carica papaya plants develop the papaya sticky disease (PSD) as a result of the combined infection of papaya meleira virus (PMeV) and papaya meleira virus 2 (PMeV2), or PMeV complex. PSD symptoms appear only after C. papaya flowers. To understand the mechanisms involved in this phenomenon, the global gene expression patterns of PMeV complex-infected C. papaya at pre-and post-flowering stages were assessed by RNA-Seq.The result was 633 and 88 differentially expressed genes at pre- and post-flowering stages, respectively. At pre-flowering stage, genes related to stress and transport were up-regulated while metabolism-related genes were down-regulated. It was observed that induction of several salicylic acid (SA)-activated genes, including PR1, PR2, PR5, WRKY transcription factors, ROS and callose genes, suggesting SA signaling involvement in the delayed symptoms. In fact, pre-flowering C. papaya treated with exogenous SA showed a tendency to decrease the PMeV and PMeV2 loads when compared to control plants. However, pre-flowering C. papaya also accumulated transcripts encoding a NPR1-inhibitor (NPR1-I/NIM1-I) candidate, genes coding for UDP-glucosyltransferases (UGTs) and several genes involved with ethylene pathway, known to be negative regulators of SA signaling. At post-flowering, when PSD symptoms appeared, the down-regulation of PR-1 encoding gene and the induction of BSMT1 and JA metabolism-related genes were observed. Hence, SA signaling likely operates at the pre-flowering stage of PMeV complex-infected C. papaya inhibiting the development of PSD symptoms, but the induction of its negative regulators prevents the full-scale and long-lasting tolerance.

The gut microbiota: A new target in the management of alcohol dependence?

The gastrointestinal tract is the natural habitat for a huge community of microorganisms, comprising bacteria, viruses, fungi and yeast. This microbial ecosystem codevelops with the host throughout life and is subject to a complex interplay that depends on multiple factors including host genetics, nutrition, life-style, stress, diseases and antibiotics use. The gut microbiota, that refers to intestinal bacteria, has profound influence on the host immune system, metabolism and nervous system. Indeed, intestinal bacteria supply the host with essential nutrients such as vitamins, metabolize bile acids and undigested compounds, defend against pathogen invasion, participate to the development of the intestinal architecture and the intestinal immune system and play an important role in the maintenance of the gut barrier function. More recently, the gut microbiota has been shown to influence brain functions, such as myelin synthesis, the blood-brain barrier permeability and neuroinflammatory responses but also mood and behavior. The cross-talk between microbes and the host implicates a vast array of signaling pathways that involve many different classes of molecules like metabolites produced by the bacteria from dietary or endogenous sources of carbohydrates and proteins (i.e. short-chain fatty acids (SCFAs), indole), neurotransmitters and inflammatory cytokines. This review will focus on the involvement of the gut microbiota in the pathophysiological aspects of alcohol dependence related to the gut barrier function, liver damage and psychological disturbances. We will also discuss the possibility to create new and realistic humanized animal models of alcohol dependence by the use of fecal transplantation.

Symposium review: Microbial endocrinology—Why the integration of microbes, epithelial cells, and neurochemical signals in the digestive tract matters to ruminant health

The union of microbiology and neurobiology, which has been termed microbial endocrinology, is defined as the study of the ability of microorganisms to produce and respond to neurochemicals that originate either within the microorganisms themselves or within the host they inhabit. It serves as the basis for an evolutionarily derived method of communication between a host and its microbiota. Mechanisms elucidated by microbial endocrinology give new insight into the ways the microbiota can affect host stress, metabolic efficiency, resistance to disease, and other factors that may prove relevant to the dairy industry.

A zebrafish model of infection-associated acute kidney injury.

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

Catecholamine-Modulated Novel Surface-Exposed Adhesin LIC20035 of Leptospira spp. Binds Host Extracellular Matrix Components and Is Recognized by the Host during Infection.

In this study, the effect of the host stress hormone catecholamine on Leptospira gene transcripts encoding outer membrane proteins was investigated. There was no impact of catecholamine supplementation on the in vitro growth pattern of Leptospira interrogans; however, 7 genes out of 41 were differentially transcribed, and the effect was reversed to the basal level in the presence of the antagonist propranolol. Comprehensive analysis of one of the differentially regulated proteins, LIC20035 (in serovar Copenhageni)/LB047 (in serovar Lai) (due to catecholamine supplementation), revealed immunogenicity and ability to adhere to host extracellular matrices. Protease accessibility assay and phase partition of integral membrane proteins of Leptospira showed LIC20035/LB047 to be an outer membrane surface-exposed protein. The recombinant LIC20035 protein can be serologically detected using human/bovine sera positive for leptospirosis. Moreover, the recombinant LIC20035 can bind to diverse host extracellular matrices, with a higher affinity toward collagen and chondroitin sulfate.IMPORTANCE Leptospirosis is a neglected tropical disease of global importance. This study aimed to identify outer membrane proteins of pathogenic Leptospira responding to host chemical signals like catecholamines, with the potential to serve as virulence factors, new serodiagnostic antigens, and vaccine candidates. This study mimicked the plausible means by which Leptospira during infection and hormonal stress intercepts host catecholamines to disseminate in host tissues.

Optimizing host cell physiology and stress avoidance for the production of recombinant human tumour necrosis factor α in Escherichia coli.

As high-level recombinant protein production (RPP) exerts a massive stress on the production host, an extensive literature on RPP optimization focuses on separating the growth phase from RPP production once sufficient biomass has been obtained. The aim of the current investigation was to optimize the benefits of the relatively neglected alternative strategy to achieve high-level RPP during growth by minimizing stress on the host. High yields of the biopharmaceutical recombinant human tumour necrosis factor alpha (rhTNFα) were obtained by fed-batch fermentation relevant to industrial production based upon parameters that most severely affected RPP in preliminary laboratory scale batch cultures. Decreasing the inducer concentration and growth temperature, but increasing the production period, were far more effective for increasing RPP yields than changing the growth phase at which production was induced. High yields of up to 5 g l-1 of rhTNFα were obtained with minimal plasmid loss, even in synthetic media that lack animal-derived components and are therefore fully compliant with regulatory requirements. Most of the product was soluble and biologically active. In summary, stress minimization was shown to be an effective way to optimize the production of rhTNFα. Data generated in shake-flask experiments allowed the design of intensified bioreactor cultures in which RPP and growth could be balanced, leading to higher yield of both rhTNFα and biomass than with previous fermentations. An additional benefit of this approach is avoidance of lysis during harvesting and downstream processing.

Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in Clinical Mycobacterium tuberculosis Isolates from Sputum, Oxidative Stress, and Iron Deficiency.

Introduction: Mycobacteria have several unique cellular characteristics, such as multiple cell envelope layers, elongation at cell poles, asymmetric cell division, and accumulation of intracytoplasmic lipid inclusions, which contributes to their survival under stress conditions. However, the understanding of these characteristics in clinical Mycobacterium tuberculosis (M. tuberculosis) isolates and under host stress is limited. We previously reported the influence of host stress on the cell length distribution in a large set of clinical M. tuberculosis isolates (n = 158). Here, we investigate the influence of host stress on the cellular ultrastructure of few clinical M. tuberculosis isolates (n = 8) from that study. The purpose of this study is to further understand the influence of host stress on the cellular adaptations of clinical M. tuberculosis isolates.Methods: We selected few M. tuberculosis isolates (n = 8) for analyzing the cellular ultrastructure ex vivo in sputum and under in vitro stress conditions by transmission electron microscopy. The cellular adaptations of M. tuberculosis in sputum were correlated with the ultrastructure of antibiotic sensitive and resistant isolates in liquid culture, under oxidative stress, iron deficiency, and exposure to isoniazid.Results: In sputum, M. tuberculosis accumulated intracytoplasmic lipid inclusions. In liquid culture, clinical M. tuberculosis revealed isolate to isolate variation in the extent of intracytoplasmic lipid inclusions, which were absent in the laboratory strain H37Rv. Oxidative stress, iron deficiency, and exposure to isoniazid increased the accumulation of lipid inclusions and decreased the thickness of the cell envelope electron transparent layer in M. tuberculosis cells. Furthermore, intracytoplasmic compartments were observed in iron deficient cells.Conclusion: Our ultrastructural analysis has revealed significant influence of host stress on the cellular adaptations in clinical M. tuberculosis isolates. These adaptations may contribute to the survival of M. tuberculosis under host and antibiotic stress conditions. Variation in the cellular adaptations among clinical M. tuberculosis isolates may correlate with their ability to persist in tuberculosis patients during antibiotic treatment. These observations indicate the need for further analyzing these cellular adaptations in a large set of clinical M. tuberculosis isolates. This will help to determine the significance of these cellular adaptations in the tuberculosis treatment.

Initial estimates of the economical attractiveness of a nuclear closed Brayton combined cycle operating with firebrick resistance-heated energy storage

Abstract The Firebrick Resistance-Heated Energy Storage (FIRES) concept developed by the Massachusetts Institute of Technology aims to enhance profitability of the nuclear power industry in the next decades. Studies carried out at Massachusetts Institute of Technology already provide estimates of the potential revenue from FIRES system when it is applied to industrial heat supply, the likely first application. Here, we investigate the possibility of operating a power plant (PP) with a fluoride-salt-cooled high-temperature reactor and a closed Brayton cycle. This variant offers features such as enhanced nuclear safety as well as flexibility in design of the PP but also radically changes the way of operating the PP. This exploratory study provides estimates of the revenue generated by FIRES in addition to the nominal revenue of the stand-alone fluoride-salt-cooled high-temperature reactor, which are useful for defining an initial design. The electricity price data is based on the day-ahead markets of Germany/Austria and the United States (Iowa). The proposed method derives from the equation of revenue introduced in this study and involves simple computations using MatLab to compute the estimates. Results show variable economic potential depending on the host grid but stress a high profitability in both regions.

Influence of Stress and Antibiotic Resistance on Cell-Length Distribution in Mycobacterium tuberculosis Clinical Isolates.

Mycobacterial cellular variations in growth and division increase heterogeneity in cell length, possibly contributing to cell-to-cell variation in host and antibiotic stress tolerance. This may be one of the factors influencing Mycobacterium tuberculosis persistence to antibiotics. Tuberculosis (TB) is a major public health problem in developing countries, antibiotic persistence, and emergence of antibiotic resistance further complicates this problem. We wanted to investigate the factors influencing cell-length distribution in clinical M. tuberculosis strains. In parallel we examined M. tuberculosis cell-length distribution in a large set of clinical strains (n = 158) from ex vivo sputum samples, in vitro macrophage models, and in vitro cultures. Our aim was to understand the influence of clinically relevant factors such as host stresses, M. tuberculosis lineages, antibiotic resistance, antibiotic concentrations, and disease severity on the cell size distribution in clinical M. tuberculosis strains. Increased cell size and cell-to-cell variation in cell length were associated with bacteria in sputum and infected macrophages rather than liquid culture. Multidrug-resistant (MDR) strains displayed increased cell length heterogeneity compared to sensitive strains in infected macrophages and also during growth under rifampicin (RIF) treatment. Importantly, increased cell length was also associated with pulmonary TB disease severity. Supporting these findings, individual host stresses, such as oxidative stress and iron deficiency, increased cell-length heterogeneity of M. tuberculosis strains. In addition we also observed synergism between host stress and RIF treatment in increasing cell length in MDR-TB strains. This study has identified some clinical factors contributing to cell-length heterogeneity in clinical M. tuberculosis strains. The role of these cellular adaptations to host and antibiotic tolerance needs further investigation.

Effect of Thermomyces fungal endophyte isolated from extreme hot desert-adapted plant on heat stress tolerance of cucumber

With the increasing effects of global climate change and population growth, there is a high need for new agricultural practices to maximize efficiencies and reduce the efforts needed for developing new crop varieties that can withstand various abiotic stress. Plant-microbe association to optimize plant growth and increase plant host stress tolerance may play an essential role in improving environmental sustainability and economic viability, especially in the arid land habitats. In the present study, photosynthetic responsiveness was selected to demonstrate that a theromophilic endophytic (CpE) fungus isolated from the hot desert-adapted delile (Cullen plicata) roots can mediate heat stress tolerance in cucumber plants grown in the field during the summer season in Egypt. Initially, the CpE isolate was identified using an internal transcribed spacer, revealing 92% sequence homology with Thermomyces sp. Then the cucumber seeds were treated with CpE endophyte spore and allowed to grow in a growth chamber for three weeks before transplanting into the field station from May to July. The CpE treatment eliminates the adverse effects of heat stress on cucumber plants by maintaining the maximum quantum efficiency of photosystem II, photosynthesis rate, water use efficiency and increase root length relative to untreated plants. In addition, CpE treatments induced the significant accumulation of total sugars, flavonoids, saponins, soluble proteins and antioxidant enzyme activities in comparison with untreated cucumber plants. Our finding provides novel insights into the eco-physiological mechanisms of thermophilic CpE-mediated heat stress tolerance in cucumber, which signify the prospective applications of arid land-adapted endophytes in agricultural systems.

HIV-1 NC-induced stress granule assembly and translation arrest are inhibited by the dsRNA binding protein Staufen1.

The nucleocapsid (NC) is an N-terminal protein derived from the HIV-1 Gag precursor polyprotein, pr55Gag. NC possesses key functions at several pivotal stages of viral replication. For example, an interaction between NC and the host double-stranded RNA-binding protein Staufen1 was shown to regulate several steps in the viral replication cycle, such as Gag multimerization and genomic RNA encapsidation. In this work, we observed that the overexpression of NC leads to the induction of stress granule (SG) assembly. NC-mediated SG assembly was unique as it was resistant to the SG blockade imposed by the HIV-1 capsid (CA), as shown in earlier work. NC also reduced host cell mRNA translation, as judged by a puromycylation assay of de novo synthesized proteins, and this was recapitulated in polysome profile analyses. Virus production was also found to be significantly reduced. Finally, Staufen1 expression completely rescued the blockade to NC-mediated SG assembly, global mRNA translation as well as virus production. NC expression also resulted in the phosphorylation of protein kinase R (PKR) and eIF2α, and this was inhibited with Staufen1 coexpression. This work sheds light on an unexpected function of NC in host cell translation. A comprehensive understanding of the molecular mechanisms by which a fine balance of the HIV-1 structural proteins NC and CA act in concert with host proteins such as Staufen1 to modulate the host stress response will aid in the development of new antiviral therapeutics.

Shrimp miR-34 from Shrimp Stress Response to Virus Infection Suppresses Tumorigenesis of Breast Cancer.

During host stress response against virus infection, some animal microRNAs (miRNAs) can be upregulated to restore the virus-caused metabolic disorder of host cells via suppressing the expressions of miRNAs’ target genes. These antiviral miRNAs may have antitumor capacity, because tumorigenesis results from metabolic disorder of cells. However, this subject has not been explored. In this study, the results showed that shrimp miR-34, which was upregulated during white spot syndrome virus (WSSV) infection, had antiviral activity in shrimp. The expression of shrimp miR-34 in breast cancer cells and in mice suppressed the growth and metastasis of breast cancer by targeting human CCND1, CDK6, CCNE2, E2F3, FOSL1, and MET genes in a cross-phylum manner. The results of this study indicated that miRNAs with antiviral activities can be promising sources for antitumor drug discovery.