- Volume 103, Issue 8, 2022
Volume 103, Issue 8, 2022
- Reviews
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DExH/D-box helicases at the frontline of intrinsic and innate immunity against viral infections
More LessDExH/D-box helicases are essential nucleic acid and ribonucleoprotein remodelers involved in all aspects of nucleic acid metabolism including replication, gene expression and post-transcriptional modifications. In parallel to their importance in basic cellular functions, DExH/D-box helicases play multiple roles in viral life cycles, with some of them highjacked by viruses or negatively regulating innate immune activation. However, other DExH/D-box helicases have recurrently been highlighted as direct antiviral effectors or as positive regulators of innate immune activation. Innate immunity relies on the ability of Pathogen Recognition Receptors to recognize viral signatures and trigger the production of interferons (IFNs) and pro-inflammatory cytokines. Secreted IFNs interact with their receptors to establish antiviral cellular reprogramming via expression regulation of the interferon-stimulated genes (ISGs). Several DExH/D-box helicases have been reported to act as viral sensors (DDX3, DDX41, DHX9, DDX1/DDX21/DHX36 complex), and others to play roles in innate immune activation (DDX60, DDX60L, DDX23). In contrast, the DDX39A, DDX46, DDX5 and DDX24 helicases act as negative regulators and impede IFN production upon viral infection. Beyond their role in viral sensing, the ISGs DDX60 and DDX60L act as viral inhibitors. Interestingly, the constitutively expressed DEAD-box helicases DDX56, DDX17, DDX42 intrinsically restrict viral replication. Hence, DExH/D-box helicases appear to form a multilayer network of primary and secondary factors involved in both intrinsic and innate antiviral immunity. In this review, we highlight recent findings on the extent of antiviral defences played by helicases and emphasize the need to better understand their immune functions as well as their complex interplay.
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Membrane architects: how positive-strand RNA viruses restructure the cell
More LessVirus infection is a process that requires combined contributions from both virus and host factors. For this process to be efficient within the crowded host environment, viruses have evolved ways to manipulate and reorganize host structures to produce cellular microenvironments. Positive-strand RNA virus replication and assembly occurs in association with cytoplasmic membranes, causing a reorganization of these membranes to create microenvironments that support viral processes. Similarities between virus-induced membrane domains and cellular organelles have led to the description of these structures as virus replication organelles (vRO). Electron microscopy analysis of vROs in positive-strand RNA virus infected cells has revealed surprising morphological similarities between genetically diverse virus species. For all positive-strand RNA viruses, vROs can be categorized into two groups: those that make invaginations into the cellular membranes (In-vRO), and those that cause the production of protrusions from cellular membranes (Pr-vRO), most often in the form of double membrane vesicles (DMVs). In this review, we will discuss the current knowledge on the structure and biogenesis of these two different vRO classes as well as comparing morphology and function of vROs between various positive-strand RNA viruses. Finally, we will discuss recent studies describing pharmaceutical intervention in vRO formation as an avenue to control virus infection.
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- Animal
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- RNA Viruses
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Thermal stabilization of enterovirus A 71 and production of antigenically stabilized empty capsids
Enterovirus A71 (EVA71) infection can result in paralysis and may be fatal. In common with other picornaviruses, empty capsids are produced alongside infectious virions during the viral lifecycle. These empty capsids are antigenically indistinguishable from infectious virus, but at moderate temperatures they are converted to an expanded conformation. In the closely related poliovirus, native and expanded antigenic forms of particle have different long-term protective efficacies when used as vaccines. The native form provides long-lived protective immunity, while expanded capsids fail to generate immunological protection. Whether this is true for EVA71 remains to be determined. Here, we selected an antigenically stable EVA71 virus population using successive rounds of heating and passage and characterized the antigenic conversion of both virions and empty capsids. The mutations identified within the heated passaged virus were dispersed across the capsid, including at key sites associated with particle expansion. The data presented here indicate that the mutant sequence may be a useful resource to address the importance of antigenic conformation in EVA71 vaccines.
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Detection of filovirus-reactive antibodies in Australian bat species
Bats have been implicated as the reservoir hosts of filoviruses in Africa, with serological evidence of filoviruses in various bat species identified in other countries. Here, serum samples from 190 bats, comprising 12 different species, collected in Australia were evaluated for filovirus antibodies. An in-house indirect microsphere assay to detect antibodies that cross-react with Ebola virus (Zaire ebolavirus; EBOV) nucleoprotein (NP) followed by an immunofluorescence assay (IFA) were used to confirm immunoreactivity to EBOV and Reston virus (Reston ebolavirus; RESTV). We found 27 of 102 Yinpterochiroptera and 19 of 88 Yangochiroptera samples were positive to EBOV NP in the microsphere assay. Further testing of these NP positive samples by IFA revealed nine bat sera that showed binding to ebolavirus-infected cells. This is the first report of filovirus-reactive antibodies detected in Australian bat species and suggests that novel filoviruses may be circulating in Australian bats.
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- DNA Viruses
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Exosomes from WSSV-infected shrimp contain viral components that mediate virus infection
More LessExosomes have been described as vesicles that mediate intercellular communication and thus affect normal and pathological processes. Furthermore, many viruses have been reported to deliver viral components to host cells through exosomes. However, the roles of exosomes in invertebrates response to virus infection are poorly understood. In this study, we found that exosomes purified from white spot syndrome virus (WSSV)-infected hemocytes of shrimp could promote viral replication. These exosomes contained WSSV genomic DNA and nucleocapsid protein VP15, suggesting that exosomes can transfer viral genetic materials between cells, although the exosomes did not have similar infection ability to viruses. Remarkably, in exosomes WSSV DNA was bound to VP15 protein, and moreover VP15 silencing significantly suppressed WSSV infection and reduced the WSSV genome fragments in exosomes, indicating that the presence of VP15 is required for the packing of WSSV DNA inside the exosomes and thereby assists virus to complete immune escape. The above results not only contribute to elucidation of the infection and transmission mechanisms of WSSV, but are also of great significance for further study of virus–host interaction and reasonable prevention measures. Taken together, our findings provide a novel insight into the regulation of virus transmission via exosomes and highlight potential therapeutic strategies.
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- Insect viruses
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- RNA
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Recovery and genetic characterization of black queen cell virus
More LessBlack queen cell virus (BQCV) is a severe threat to the honeybee (Apis mellifera) worldwide. Although several BQCV strains have been reported in China, the molecular basis for BQCV pathogenicity has not been well understood. Thus, a reverse genetic system of BQCV is required for studying viral replication and its pathogenic mechanism. Here, the complete genome sequence of BQCV was obtained from honeybees using reverse transcription PCR (RT-PCR), namely a BQCV China-GS1 strain (KY741959). Then, a phylogenetic tree was built to analyse the genetic relationships among BQCV strains from different regions. Our results showed that the BQCV China-GS1 contained two ORFs, consistent with the known reference strains, except for the BQCV China-JL1 strain (KP119603). Furthermore, the infectious clone of BQCV was constructed based on BQCV China-GS1 using a low copy vector pACYC177 and gene recombination. Due to the lack of culture cells for bee viruses, we infected the healthy bees with infectious clone of BQCV, and the rescued BQCV resulted in the recovery of recombinant virus, which induced higher mortality than those of the control group. Immune response after inoculated with BQCV further confirmed that the infectious clone of BQCV caused the cellular and humoral immune response of honeybee (A. mellifera). In conclusion, the full nucleotide sequence of BQCV China-GS1 strain was determined, and the infectious clone of BQCV was constructed in this study. These data will improve the understanding of pathogenesis and the host immune responses to viral infection.
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Knockout of Dicer-2 in the Sf9 cell line enhances the replication of Spodoptera frugiperda rhabdovirus and conditionally increases baculovirus replication
More LessThe Sf9 cell line, originally isolated from the ovarian tissue of Spodoptera frugiperda larvae, is widely used in academia and industry for the baculovirus-mediated production of recombinant proteins and virus-like particles. RNA interference (RNAi) is a conserved antiviral pathway present in eukaryotic organisms and is the primary antiviral defence mechanism in insects. Recent evidence has implicated RNAi as an antiviral response to baculovirus infection in Sf9 cells. To test this hypothesis, CRISPR/Cas9 technology was used to disable the RNAi pathway in Sf9 cells by knocking out Dicer-2, the protein responsible for cleaving viral double-stranded RNA precursors into short interfering RNAs. Infection of Dicer-2 knockout Sf9 cells with either the wild-type baculovirus Autographa californica nucleopolyhedrovirus (AcMNPV), recombinant AcMNPV (rAcMNPV) expressing β-galactosidase (β-gal), or rAcMNPV expressing a wasp venom protein (Vn50) at a multiplicity of infection (m.o.i.) of 1 resulted in a modest increase in virus replication compared to control Sf9 cells under adherent culture conditions. In contrast, Dicer-2 knockout Sf9 monolayer or suspension cultures infected by the rAcMNPV expressing β-gal at higher m.o.i.s (3.5 and 20) did not exhibit increases in either viral DNA replication or β-gal production. Intriguingly, during long-term passaging in suspension, Dicer-2 knockout Sf9 cultures underwent transient crashes in cell proliferation and viability. It was discovered that these periods of low growth and viability coincided with a dramatic increase in the RNA levels of S. frugiperda rhabdovirus, a recently identified adventitious virus that persistently infects the Sf9 cell line, suggesting a role for Dicer-2 in managing chronic viral infections in this industrially relevant insect cell line.
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- Plant
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- RNA viruses
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Cap-snatching as a possible contributor to photosynthesis shut-off
More LessCap-snatching is a mechanism applied by segmented, negative strand (-) RNA viruses (NSVs) to initiate genome transcription. So far, the cap donor source of cytoplasmic-replicating NSVs has remained elusive. Recently, studies pointed to processing body (P body, PB) as the potential source for providing capped RNAs but conclusive evidence is still lacking. To attempt identifying these sources, here the 5′ non-viral leader sequences of Tomato spotted wilt virus (TSWV) N mRNAs were analysed by high-throughput sequencing (HTS) from plants subjected to normal and heat-stress conditions, and subsequently mapped on host donor transcripts. The majority of non-viral heterogenous, host-derived leader sequences ranged in size between ~10–20 nt and contained A or AG residues at the cleavage site and the presence of certain sequence motifs. Mapping the capped-leader sequences to the 5’ UTR region of genes encoded by the Nicotiana tabacum genome, identified 348 donor genes and which were specifically enriched in cellular photosynthesis pathway. Nineteen of those were clearly expressed differentially at normal condition versus heat-stress conditions. Although the results did not point towards snatching of capped-RNA leader sequences from certain cytoplasmic RNA granules in particular, they indicated photosynthesis downregulation (and development of disease symptoms) partially result from cap-snatching.
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Comparative analysis of virus pathogenicity and resistance-breaking between the P- and A-type from the beet necrotic yellow vein virus using infectious cDNA clones
More LessThe A-type of beet necrotic yellow vein virus (BNYVV) is widely distributed in Europe and is one of the major virus types causing rhizomania disease in sugar beet. The closely related P-type is mainly limited to a small region in France (Pithiviers). Both virus types possess four RNAs (RNA1–4), but the P-type harbours an additional fifth RNA species (RNA5). The P-type is associated with stronger disease symptoms and resistance-breaking of Rz1, one of the two resistance genes which are used to control BNYVV infection. These characteristics are presumably due to the presence of RNA5, but experimental evidence for this is lacking. We generated the first infectious cDNA clone of BNYVV P-type to study its pathogenicity in sugar beet in comparison to a previously developed A-type clone. Using this tool, we confirmed the pathogenicity of the P-type clone in the experimental host Nicotiana benthamiana and two Beta species, B. macrocarpa and B. vulgaris. Independent of RNA5, both the A- and the P-type accumulated in lateral roots and reduced the taproot weight of a susceptible sugar beet genotype to a similar extent. In contrast, only the P-type clone was able to accumulate a virus titre in an Rz1-resistant variety whereas the A-type clone failed to infect this variety. The efficiency of the P-type to overcome Rz1 resistance was strongly associated with the presence of RNA5. Only a double resistant variety, harbouring Rz1 and Rz2, prevented an infection with the P-type. Reassortment experiments between the P- and A-type clones demonstrated that both virus types can exchange whole RNA components without losing the ability to replicate and to move systemically in sugar beet. Although our study highlights the close evolutionary relationship between the two virus types, we were able to demonstrate distinct pathogenicity properties that are attributed to the presence of RNA5 in the P-type.
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- Phage (prokaryotic viruses)
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Insights into the human gut virome by sampling a population from the Indian subcontinent
More LessGut virome plays an important role in human physiology but remains poorly understood. This study reports an investigation of the human gut DNA-virome of a previously unexplored ethnic population through metagenomics of faecal samples collected from individuals residing in Northern India. Analysis shows that, similar to the populations investigated earlier, majority of the identified virome belongs to bacteriophages and a smaller fraction (<20 %) consists of viruses that infect animals, archaea, protists, multiple domains or plants. However, crAss-like phages, in this population, are dominated by the genera VI, VII and VIII. Interestingly, it also reveals the presence of a virus family, Sphaerolipoviridae, which has not been detected in the human gut earlier. Viral families, Siphoviridae, Myoviridae, Podoviridae, Microviridae, Herelleviridae and Phycodnaviridae are detected in all of the analysed individuals, which supports the existence of a core virome. Lysogeny-associated genes were found in less than 10 % of the assembled genomes and a negative correlation was observed in the richness of bacterial and free-viral species, suggesting that the dominant lifestyle of gut phage is not lysogenic. This is in contrast to some of the earlier studies. Further, several hundred high-quality viral genomes were recovered. Detailed characterization of these genomes would be useful for understanding the biology of these viruses and their significance in human physiology.
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Volumes and issues
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Volume 105 (2024)
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Volume 104 (2023)
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Volume 103 (2022)
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Volume 102 (2021)
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Volume 101 (2020)
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Volume 100 (2019)
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Volume 99 (2018)
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Volume 98 (2017)
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Volume 97 (2016)
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Volume 96 (2015)
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Volume 95 (2014)
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Volume 94 (2013)
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Volume 93 (2012)
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Volume 92 (2011)
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Volume 91 (2010)
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Volume 90 (2009)
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Volume 89 (2008)
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Volume 88 (2007)
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Volume 87 (2006)
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Volume 86 (2005)
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Volume 85 (2004)
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Volume 84 (2003)
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Volume 83 (2002)
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Volume 82 (2001)
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Volume 81 (2000)
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Volume 80 (1999)
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Volume 79 (1998)
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Volume 78 (1997)
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Volume 77 (1996)
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Volume 76 (1995)
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Volume 75 (1994)
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Volume 74 (1993)
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Volume 73 (1992)
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Volume 72 (1991)
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Volume 71 (1990)
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Volume 70 (1989)
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Volume 69 (1988)
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Volume 68 (1987)
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Volume 67 (1986)
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Volume 66 (1985)
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Volume 65 (1984)
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Volume 64 (1983)
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Volume 63 (1982)
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Volume 62 (1982)
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Volume 61 (1982)
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Volume 60 (1982)
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Volume 59 (1982)
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Volume 58 (1982)
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Volume 57 (1981)
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Volume 56 (1981)
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Volume 55 (1981)
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Volume 54 (1981)
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Volume 53 (1981)
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Volume 52 (1981)
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Volume 51 (1980)
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Volume 50 (1980)
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Volume 49 (1980)
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Volume 48 (1980)
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Volume 47 (1980)
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Volume 46 (1980)
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Volume 45 (1979)
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Volume 44 (1979)
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Volume 43 (1979)
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Volume 42 (1979)
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Volume 41 (1978)
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Volume 40 (1978)
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Volume 39 (1978)
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Volume 38 (1978)
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Volume 37 (1977)
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Volume 36 (1977)
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Volume 35 (1977)
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Volume 34 (1977)
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Volume 33 (1976)
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Volume 32 (1976)
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Volume 31 (1976)
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Volume 30 (1976)
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Volume 29 (1975)
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Volume 28 (1975)
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Volume 27 (1975)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1974)
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Volume 23 (1974)
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Volume 22 (1974)
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Volume 21 (1973)
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Volume 20 (1973)
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Volume 19 (1973)
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Volume 18 (1973)
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Volume 17 (1972)
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Volume 16 (1972)
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Volume 15 (1972)
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Volume 14 (1972)
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Volume 13 (1971)
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Volume 12 (1971)
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Volume 11 (1971)
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Volume 10 (1971)
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Volume 9 (1970)
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Volume 8 (1970)
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Volume 7 (1970)
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Volume 6 (1970)
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Volume 5 (1969)
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Volume 4 (1969)
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Volume 3 (1968)
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Volume 2 (1968)
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Volume 1 (1967)