Host Cellular Environment Research Articles

Strategies for Survival of Staphylococcus aureus in Host Cells.

Staphylococcus aureus, a common pathogen, is capable of producing a significant array of toxins and can develop biofilms or small colony variants (SCVs) to evade detection by the immune system and resist the effects of antibiotics. Its ability to persist for extended periods within host cells has led to increased research interest. This review examines the process of internalization of S. aureus, highlighting the impact of its toxins and adhesion factors on host cells. It elucidates the intricate interactions between them and the host cellular environment, thereby offering potential strategies for the treatment and prevention of S. aureus infections.

Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal.

Sub-Saharan Africa accounts for almost 70% of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98% of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12% of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus. Furthermore, the impact of genetic variation between viral subtypes, specifically within the long terminal repeat (LTR) element of the viral transcriptional promoter on latency reversal, remains unclear. To address this scientific gap, we constructed a minimal genome retroviral vector expressing HIV-1C consensus transactivator of transcription protein (Tat) and green fluorescent protein (GFP) under the control of either HIV-1C consensus LTR (C731CC) or the transmitted/founder (T/F) LTRs derived from PLWH (CT/F731CC), produced corresponding LTR pseudotyped viruses using a vesicular stomatitis virus (VSV-G) pseudotyped Envelope vector and the pCMVΔR8.91 packaging vector containing HIV-1 accessory and rev genes. Viruses produced in this way were used to infect Jurkat E6 and primary CD4+ T cells in vitro. By enriching for latently infected cells, and treating them with different latency reversing agents, we developed an HIV-1C latency model that demonstrated that the HIV-1C consensus LTR has lower reactivation potential compared to its HIV-1B counterpart. Furthermore, HIV-1C T/F LTR pseudotyped proviral genetic variants exhibited a heterogenous reactivation response which was modulated by host cell (genetic) variation. Our data suggests that genetic variation both within and between HIV-1 subtypes influences latency reversal. Future studies should investigate the specific role of variation in host cellular environment on reactivation differences.

Triggering Degradation of Host Cellular Proteins for Robust Propagation of Influenza Viruses.

Following infection, influenza viruses strive to establish a new host cellular environment optimized for efficient viral replication and propagation. Influenza viruses use or hijack numerous host factors and machinery not only to fulfill their own replication process but also to constantly evade the host's antiviral and immune response. For this purpose, influenza viruses appear to have formulated diverse strategies to manipulate the host proteins or signaling pathways. One of the most effective tactics is to specifically induce the degradation of the cellular proteins that are detrimental to the virus life cycle. Here, we summarize the cellular factors that are deemed to have been purposefully degraded by influenza virus infection. The focus is laid on the mechanisms for the protein ubiquitination and degradation in association with facilitated viral amplification. The fate of influenza viral infection of hosts is heavily reliant on the outcomes of the interplay between the virus and the host antiviral immunity. Understanding the processes of how influenza viruses instigate the protein destruction pathways could provide a foundation for the development of advanced therapeutics to target host proteins and conquer influenza.

Mycobacterium tuberculosis EspR modulates Th1-Th2 shift by transcriptionally regulating IL-4, steering increased mycobacterial persistence and HIV propagation during co-infection.

Mycobacterium tuberculosis (Mtb) and HIV are known to mutually support each other during co-infection by multiple mechanisms. This synergistic influence could be either by direct interactions or indirectly through secreted host or pathogen factors that work in trans. Mtb secretes several virulence factors to modulate the host cellular environment for its persistence and escaping cell-intrinsic immune responses. We hypothesized that secreted Mtb transcription factors that target the host nucleus can directly interact with host DNA element(s) or HIV LTR during co-infection, thereby modulating immune gene expression, or driving HIV transcription, helping the synergistic existence of Mtb and HIV. Here, we show that the Mtb-secreted protein, EspR, a transcription regulator, increased mycobacterial persistence and HIV propagation during co-infection. Mechanistically, EspR localizes to the nucleus of the host cells during infection, binds to its putative cognate motif on the promoter region of the host IL-4 gene, activating IL-4 gene expression, causing high IL-4 titers that induce a Th2-type microenvironment, shifting the macrophage polarization to an M2 state as evident from CD206 dominant population over CD64. This compromised the clearance of the intracellular mycobacteria and enhanced HIV propagation. It was interesting to note that EspR did not bind to HIV LTR, although its transient expression increased viral propagation. This is the first report of an Mtb transcription factor directly regulating a host cytokine gene. This augments our understanding of the evolution of Mtb immune evasion strategies and unveils how Mtb aggravates comorbidities, such as HIV co-infection, by modulating the immune microenvironment.

Genomic Assessment of the Contribution of the Wolbachia Endosymbiont of Eurosta solidaginis to Gall Induction.

We explored the genome of the Wolbachia strain, wEsol, symbiotic with the plant-gall-inducing fly Eurosta solidaginis with the goal of determining if wEsol contributes to gall induction by its insect host. Gall induction by insects has been hypothesized to involve the secretion of the phytohormones cytokinin and auxin and/or proteinaceous effectors to stimulate cell division and growth in the host plant. We sequenced the metagenome of E. solidaginis and wEsol and assembled and annotated the genome of wEsol. The wEsol genome has an assembled length of 1.66 Mbp and contains 1878 protein-coding genes. The wEsol genome is replete with proteins encoded by mobile genetic elements and shows evidence of seven different prophages. We also detected evidence of multiple small insertions of wEsol genes into the genome of the host insect. Our characterization of the genome of wEsol indicates that it is compromised in the synthesis of dimethylallyl pyrophosphate (DMAPP) and S-adenosyl L-methionine (SAM), which are precursors required for the synthesis of cytokinins and methylthiolated cytokinins. wEsol is also incapable of synthesizing tryptophan, and its genome contains no enzymes in any of the known pathways for the synthesis of indole-3-acetic acid (IAA) from tryptophan. wEsol must steal DMAPP and L-methionine from its host and therefore is unlikely to provide cytokinin and auxin to its insect host for use in gall induction. Furthermore, in spite of its large repertoire of predicted Type IV secreted effector proteins, these effectors are more likely to contribute to the acquisition of nutrients and the manipulation of the host's cellular environment to contribute to growth and reproduction of wEsol than to aid E. solidaginis in manipulating its host plant. Combined with earlier work that shows that wEsol is absent from the salivary glands of E. solidaginis, our results suggest that wEsol does not contribute to gall induction by its host.

Natural Populations from the Phytophthora palustris Complex Show a High Diversity and Abundance of ssRNA and dsRNA Viruses.

We explored the virome of the "Phytophthora palustris complex", a group of aquatic specialists geographically limited to Southeast and East Asia, the native origin of many destructive invasive forest Phytophthora spp. Based on high-throughput sequencing (RNAseq) of 112 isolates of "P. palustris" collected from rivers, mangroves, and ponds, and natural forests in subtropical and tropical areas in Indonesia, Taiwan, and Japan, 52 putative viruses were identified, which, to varying degrees, were phylogenetically related to the families Botybirnaviridae, Narnaviridae, Tombusviridae, and Totiviridae, and the order Bunyavirales. The prevalence of all viruses in their hosts was investigated and confirmed by RT-PCR. The rich virus composition, high abundance, and distribution discovered in our study indicate that viruses are naturally infecting taxa from the "P. palustris complex" in their natural niche, and that they are predominant members of the host cellular environment. Certain Indonesian localities are the viruses' hotspots and particular "P. palustris" isolates show complex multiviral infections. This study defines the first bi-segmented bunya-like virus together with the first tombus-like and botybirna-like viruses in the genus Phytophthora and provides insights into the spread and evolution of RNA viruses in the natural populations of an oomycete species.

Isolation of Protein Complexes from Tobacco Leaves by a Two-Step Tandem Affinity Purification.

Protein purification is an essential method for understanding protein function, as many biochemical and structural techniques require a high concentration of isolated protein for analysis. Yet, many studies of protein complexes are hampered by our inability to express them recombinantly in model systems, generally due to poor expression or aggregation. When studying a protein complex that requires its host cellular environment for proper expression and folding, endogenous purification is typically required. Depending on the protein of interest, however, endogenous purification can be challenging because of low expression levels in the host and lack of knowledge working with a non-model expression system, resulting in yields that are too low for subsequent analysis. Here, we describe a protocol for the purification of protein complexes endogenous to Nicotiana benthamiana directly from leaf tissue, with yields that enable structural and biochemical characterization. The protein complex is overexpressed in Nicotiana benthamiana leaves via agroinfiltration, and the protein-packed leaves are then mechanically ground to release the complex from the cells. The protein complex is finally purified by a simple two-step tandem affinity purification using distinct affinity tags for each complex member, to ensure purification of the assembled complex. Our method yields enough protein for various biochemical or structural studies. We have previously used this protocol to purify the complex formed by an innate immune receptor native to tobacco, ROQ1, and the Xanthomonas effector XopQ, and to solve its structure by single-particle cryo-electron microscopy-we use this example to illustrate the approach. This protocol may serve as a template for the purification of proteins from N. benthamiana that require the plant's cellular environment and are expressed at low levels. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Expression of the protein complex in leaf tissue Basic Protocol 2: Tandem affinity purification of the ROQ1-XopQ complex.

Human Cytomegalovirus UL24 and UL43 Cooperate to Modulate the Expression of Immunoregulatory UL16 Binding Protein 1.

The human cytomegalovirus (HCMV) UL24 and UL43 are tegument proteins that have recently been shown to interact with each other in a yeast two-hybrid system. By their overexpression in MRC5 cells, we demonstrate that these viral proteins interact with several important host proteins, especially Dicer and trans-activation response RNA binding protein. As these hots proteins are involved in regulating the production of cellular micro-RNAs, the cytomegalovirus (CMV) proteins could interfere with their actions to favor viral replication directly or through an immune escape mechanism. Double knockout of UL24 and UL43 does not show a remarkable effect on CMV entry or replication, but it significantly downregulates the expression of CMV-encoded miR-UL59, which is thought to regulate the expression of a downstream target UL16 binding protein 1 (ULBP1). Interestingly, the double knockout increases the expression of the ULBP1 recognized by the NKG2D activating receptor of natural killer cells. This study investigates the potential role of several proteins encoded by HCMV in regulating the host cellular environment to favor escape from immunity, and it also provides some basis for the future development of RNA-targeted small molecules to control HCMV infection.

Transcriptomic responses of Galápagos finches to avian poxvirus infection.

Emerging pathogens can have devastating effects on naïve hosts, but disease outcomes often vary among host species. Comparing the cellular response of different hosts to infection can provide insight into mechanisms of host defence. Here, we used RNA-seq to characterize the transcriptomic response of Darwin's finches to avian poxvirus, a disease of concern in the Galápagos Islands. We tested whether gene expression differs between infected and uninfected birds, and whether transcriptomic differences were related either to known antiviral mechanisms and/or the co-option of the host cellular environment by the virus. We compared two species, the medium ground finch (Geospiza fortis) and the vegetarian finch (Platyspiza crassirostris), to determine whether endemic Galápagos species differ in their response to pox. We found that medium ground finches had a strong transcriptomic response to infection, upregulating genes involved in the innate immune response including interferon production, inflammation, and other immune signalling pathways. In contrast, vegetarian finches had a more limited response, and some changes in this species were consistent with viral manipulation of the host's cellular function and metabolism. Many of the transcriptomic changes mirrored responses documented in model and in vitro studies of poxviruses. Our results thus indicate that many pathways of host defence against poxviruses are conserved among vertebrates and present even in hosts without a long evolutionary history with the virus. At the same time, the differences we observed between closely related species suggests that some endemic species of Galápagos finch could be more susceptible to avian pox than others.

Rotavirus activates MLKL-mediated host cellular necroptosis concomitantly with apoptosis to facilitate dissemination of viral progeny.

Reprogramming the host cellular environment is an obligatory facet of viral pathogens to foster their replication and perpetuation. One of such reprogramming events is the dynamic cross-talk between viruses and host cellular death signaling pathways. Rotaviruses (RVs) have been reported to develop multiple mechanisms to induce apoptotic programmed cell death for maximizing viral spread and pathogenicity. However, the importance of non-apoptotic programmed death events has remained elusive in context of RV infection. Here, we report that RV-induced apoptosis accompanies another non-apoptotic mode of programmed cell death pathway called necroptosis to promote host cellular demise at late phase of infection. Phosphorylation of mixed lineage kinase domain-like (MLKL) protein indicative of necroptosis was observed to concur with caspase-cleavage (apoptotic marker) beyond 6hr of RV infection. Subsequent studies demonstrated phosphorylated-MLKL to oligomerize and to translocate to plasma membrane in RV infected cells, resulting in loss of plasma membrane integrity and release of alarmin molecules e.g., high mobility group box protein 1 (HMGB1) in the extracellular media. Moreover, inhibiting caspase-cleavage and apoptosis could not fully rescue virus-induced cell death but rather potentiated the necroptotic trigger. Interestingly, preventing both apoptosis and necroptosis by small molecules significantly rescued virus-induced host cytopathy by inhibiting viral dissemination.

Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process

The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable to de novo genetic diversity that emerges through mutations in RNA. Although the molecular spectrum of de novo mutations—the relative rates at which various base substitutions occur—are widely recognized as informative toward understanding the evolution of a viral genome, little attention has been paid to the possibility of using molecular spectra to infer the host origins of a virus. Here, we characterize the molecular spectrum of de novo mutations for SARS-CoV-2 from transcriptomic data obtained from virus-infected cell lines, enabled by the use of sporadic junctions formed during discontinuous transcription as molecular barcodes. We find that de novo mutations are generated in a replication-independent manner, typically on the genomic strand, and highly dependent on mutagenic mechanisms specific to the host cellular environment. De novo mutations will then strongly influence the types of base substitutions accumulated during SARS-CoV-2 evolution, in an asymmetric manner favoring specific mutation types. Consequently, similarities between the mutation spectra of SARS-CoV-2 and the bat coronavirus RaTG13, which have accumulated since their divergence strongly suggest that SARS-CoV-2 evolved in a host cellular environment highly similar to that of bats before its zoonotic transfer into humans. Collectively, our findings provide data-driven support for the natural origin of SARS-CoV-2.

The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation.

Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the causal factor in over 99 % of cervical cancer cases, and a significant proportion of oropharyngeal and anogenital cancers. The key drivers of HPV-mediated transformation are the oncoproteins E5, E6 and E7. Together, they act to prolong cell-cycle progression, delay differentiation and inhibit apoptosis in the host keratinocyte cell in order to generate an environment permissive for viral replication. The oncoproteins also have key roles in mediating evasion of the host immune response, enabling infection to persist. Moreover, prolonged infection within the cellular environment established by the HR-HPV oncoproteins can lead to the acquisition of host genetic mutations, eventually culminating in transformation to malignancy. In this review, we outline the many ways in which the HR-HPV oncoproteins manipulate the host cellular environment, focusing on how these activities can contribute to carcinogenesis.

A Xanthomonas oryzae type III effector XopL causes cell death through mediating ferredoxin degradation in Nicotiana benthamiana

Plant pathogenic bacteria engage in an ongoing struggle for survival. Gram negative phytopathogenic prokaryotes deploy type III secretion system to deliver effector proteins into plant cells to manipulate the host cellular environment. In many cases, the targets of these effector proteins are unknown. The bacterial blight pathogen, Xanthomonas oryzae pv. oryzae (Xoo), causes a devastating disease in rice and the Xoo-rice interaction is an example of the ongoing evolutionary battle between plants and pathogens. In this study, we show that an effector XopL from Xoo exhibits E3 ubiquitin ligase activity and induces cell death in the nonhost Nicotiana benthamiana (Nb). Through yeast two-hybrid, co-immunoprecipitation, and biomolecular fluorescence complementation assays, it was shown that XopL interacts with ferredoxin (NbFd), an electron transport molecule in plant chloroplasts. XopL induced defense-related response in Nb and specifically targeted NbFd for ubiquitination and ubiquitin-mediated degradation, a process that increased the production of reactive oxygen species (ROS). This study demonstrates the ubiquitination and degradation of NbFd as a result of XopL activity, which further illustrates the tremendous functional diversity in Xanthomonas effector proteins.

The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick diseasetype C, with therapeutic implications.

Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID‐19. By describing the life cycle of the newly emergent coronavirus, SARS‐CoV‐2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID‐19. Moreover, we propose that Niemann‐Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS‐CoV‐2, by highlighting key established features of the disorder that together result in an “unfavorable” host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID‐19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC‐like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID‐19.

Glucose-6-phosphate dehydrogenase deficiency enhances Covid-19 infection in elderly people.

Our understanding of the mechanisms responsible for death of aged people from Covid-19 became one of the major concerns of these days. Glucose-6-phosphate dehydrogenase (G6PD) enhances the normal senescence and accelerates the precocious removal of chronologically young, yet biologically aged cells. Thus, its deficiency is associated with an increase in the cellular oxidative stress. Accumulating evidence showed that oxidative stress has a fundamental role in several age-related diseases. Nowadays, Covid-19 is considered a serious health problem worldwide. The host cellular environment is the key determinant of pathogen Infectivity. Most respiratory viral infections have a strong association with Glucose-6-phosphate dehydrogenase. Unfortunately, this enzyme deficiency markedly decreases with aging what is involved in increasing of the morbidity rate. The aim of this mini review was to shed more light on the role of G6PD deficiency in aged people infected with Covid-19 (Ref. 20). Keywords: GSPD, Covid-19, elderly people.

Modulation of host immune status by cryptococcus co-infection during HIV-1 pathogenesis and its impact on CD+4 cell and cytokines environment

BackgroundCryptococcus infection is the second most common opportunistic infection in HIV patients with an increased rate of morbidity and mortality. Altered immune system during HIV- Cryptococcus co-infection is yet to be explored by laboratory. This study evaluates pro- and the anti-inflammatory cytokines in HIV patients with Cryptococcus co-infection and correlate them with CD4+T cell counts as well as viral loads before the initiation of drug therapy. This information would enable to understand host immune modulation and cellular environment during co-infection and understand its impact on HIV pathogenesis. MethodologyThe study comprised four categories of patients with cryptococcosis, HIV, HIV-cryptococcosis co-infected and asymptomatic Healthy volunteers. All the patients and healthy individuals were subjected to CD4+T cells count by FACS using monoclonal antibody cocktail CD4+T cell count (counts per mm3) which was counted using multiSET software on FACS caliber. The viral loads were counted in terms of viral RNA copy numbers which was estimated by real-time PCR using by Artus HIV-1 RG. The sensitivity of kit was >70 IU/ml. ELISA was performed for IL-12 p70, IL-12, IL-4, IL-10, IL-6, TNF-α and IFN-Y using commercially kits (BD Biosciences, USA). Significant variations were assayed by Student's t-test and P values ≤ 0.05 were considered statistically significant. ResultsReduction in CD+4 cell counts was highly significant in HIV patients with or without cryptococcosis. CD4+T cell counts were inversely proportional to viral load. TNF-α levels were raised in cryptococcosis patients significantly higher than healthy individuals. TNF-α was more or less not dependent on viral load but it was more related to the cryptococcosis IL-12 levels were increased in patients with infection and was highest in the HIV infected group. Level of IL-4 was similar in healthy and patients with cryptococcosis but it was elevated in HIV-Crypto co-infected patients. HIV infected patients showed a significant increase in IL-4 level and it was elevated higher in co-infected patients. IL-10 and IL-6 were significantly higher in HIV patients. The fungal infection did not influence the levels of IL-10 in HIV group but IL-6 was low in fungal infected patients. ConclusionThere are very limited studies related to the immune modulation status of HIV co-infected with Cryptococcus before the initiation of any drug therapy. Such information might through in-depth light to understand the initial state of the immune environment which certainly would play a pivotal role in the outcome of the immune modulation.

Intrinsically Disordered Human T Lymphotropic Virus Type 1 p30 Protein: Experimental and Computational Evidence.

Human T lymphotropic virus type 1 (HTLV-1) causes adult T cell leukemia and lymphoma and other neuroinflammatory diseases. The pX region of HTLV-1 genome encodes an accessory protein p30 that is required for viral persistence and spread in the host. p30 regulates viral gene expression at the transcription level by competing with Tax for p300 binding and at posttranscriptional level by nuclear retention of tax/rex messenger RNA (mRNA). In addition, p30 modulates the host cellular environment by binding to various host proteins such as ATM, REGγ, and PRMT5. However, the low expression levels of p30 has been a major hurdle in studying its structure-function relationship in the context of HTLV-1 pathobiology, which is most likely due to its intrinsically disordered nature. To investigate the unstable nature of p30, flow cytometric analysis of p30-GFP fusion protein expressed in Escherichia coli was conducted and bioinformatics analysis of p30 was performed. The bacterial cells were green fluorescent protein (GFP) positive, indicating that p30-GFP was in the soluble fraction. Induction, particularly at higher temperature, reduced the expression of p30-GFP. Moreover, p30-GFP was detected exclusively in insoluble fraction upon cell lysis, suggesting its unstable and disordered nature. The bioinformatics analysis of p30 protein sequence and amino acid content revealed that p30 has highly disordered regions from amino acids 75-155 and 197-241. Furthermore, p30 has regions for macromolecular interactions that could stabilize it and these regions coincide with the unstable regions. Collectively, the study indicates that HTLV-1 p30 is an intrinsically disordered protein.

Focus on Translation Initiation of the HIV-1 mRNAs.

To replicate and disseminate, viruses need to manipulate and modify the cellular machinery for their own benefit. We are interested in translation, which is one of the key steps of gene expression and viruses that have developed several strategies to hijack the ribosomal complex. The type 1 human immunodeficiency virus is a good paradigm to understand the great diversity of translational control. Indeed, scanning, leaky scanning, internal ribosome entry sites, and adenosine methylation are used by ribosomes to translate spliced and unspliced HIV-1 mRNAs, and some require specific cellular factors, such as the DDX3 helicase, that mediate mRNA export and translation. In addition, some viral and cellular proteins, including the HIV-1 Tat protein, also regulate protein synthesis through targeting the protein kinase PKR, which once activated, is able to phosphorylate the eukaryotic translation initiation factor eIF2α, which results in the inhibition of cellular mRNAs translation. Finally, the infection alters the integrity of several cellular proteins, including initiation factors, that directly or indirectly regulates translation events. In this review, we will provide a global overview of the current situation of how the HIV-1 mRNAs interact with the host cellular environment to produce viral proteins.

The parasitic plant haustorium: a trojan horse releasing microRNAs that take control of the defense responses of the host

Organisms in a symbiotic relationship have evolved in an arms race to modulate each other’s physiology. In most cases, symbiotic interactions elicit a local and a systemic response that involves an extensive transcriptional reprogramming of both organisms. Although the genetic component of these interactions has been studied for years, the potential exchange of genetic information between symbionts has remained elusive till now. The theory that an exchange of RNA could exist was an exciting, yet difficult-to-prove, theory. However, in recent years, due to both the development of high-throughput sequencing and increase in genome sequence information, it has been confirmed that both messenger RNAs (mRNAs) and small RNAs (sRNAs) are exchanged between symbionts. Most strikingly, these foreign sRNAs are functional in the host cellular environment and, in most of the cases, they are involved in the regulation of pathogenicity and virulence. Here, we review the recent discovery of the exchange of sRNAs between a parasitic plant, Cuscuta campestris , and its host Arabidopsis thaliana (1), which opens new perspectives and questions both at the agricultural and biological levels.

Human cytomegalovirus miR-US5-1 inhibits viral replication by targeting Geminin mRNA.

Viruses commonly create favorable cellular conditions for their survival through multiple mechanisms. MicroRNAs (miRNAs), which function as post-transcriptional regulators, are utilized by human cytomegalovirus (HCMV) in its infection and pathogenesis. In the present study, the DNA replication inhibitor Geminin (GMNN) was identified to be a direct target of hcmv-miR-US5-1. Overexpression of hcmv-miR-US5-1 could block the accumulation of GMNN during HCMV infection, and the decrease of GMNN expression caused by hcmv-miR-US5-1 or GMNN specific siRNA reduced HCMV DNA copies in U373 cells. Meanwhile, ectopic expression of hcmv-miR-US5-1 and consequent lower expression of GMNN influenced host cell cycle and proliferation. These results imply that hcmv-miR-US5-1 may affect viral replication and host cellular environment by regulating expression kinetics of GMNN during HCMV infection.