Four amino acids of an insect densovirus capsid determine midgut tropism and virulence.
Ontology highlight
ABSTRACT:
SUBMITTER: Multeau C
PROVIDER: S-EPMC3347284 | biostudies-literature | 2012 May
REPOSITORIES: biostudies-literature
Publications
Four amino acids of an insect densovirus capsid determine midgut tropism and virulence.
Multeau Cecilia C Froissart Rémy R Perrin Aurélie A Castelli Ilaria I Casartelli Morena M Ogliastro Mylène M
Journal of virology 20120229 10
Densoviruses are insect parvoviruses that are orally infectious for Lepidoptera. To assess the mechanisms underlying their specificity and their virulence, we investigated the role of eight candidate residues in the densovirus capsid. We showed that the substitutions of four amino acids were associated with decreased virulence due to a decreased ability to cross the host midgut epithelium, without an effect on viral replication in other tissues. ...[more]
Similar Datasets
Project description:Densoviruses are parvoviruses that can be lethal for insects of different orders at larval stages. Although the horizontal transmission mechanisms are poorly known, densoviral pathogenesis usually starts with the ingestion of contaminated food by the host. Depending on the virus, this leads to replication restricted to the midgut or excluding it. In both cases the success of infection depends on the virus capacity to enter the intestinal epithelium. Using the Junonia coenia densovirus (JcDNV) as the prototype virus and the lepidopteran host Spodoptera frugiperda as an interaction model, we focused on the early mechanisms of infection during which JcDNV crosses the intestinal epithelium to reach and replicate in underlying target tissues. We studied the kinetics of interaction of JcDNV with the midgut epithelium and the transport mechanisms involved. Using several approaches, in vivo, ex vivo, and in vitro, at molecular and cellular levels, we show that JcDNV is specifically internalized by endocytosis in absorptive cells and then crosses the epithelium by transcytosis. As a consequence, viral entry disturbs the midgut function. Finally, we showed that four mutations on the capsid of JcDNV affect specific recognition by the epithelial cells but not their binding.
| S-EPMC3807927 | biostudies-literature
Project description:HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5) viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences) and genotypic (e.g., population sequencing linked to bioinformatic algorithms) assays are the most widely used. Although several next-generation sequencing (NGS) platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences), Illumina®, and Ion Torrent™ (Life Technologies). Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels) and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%). In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.
| S-EPMC3498215 | biostudies-literature
Project description:Densovirus genome replication and capsid assembly take place in the nucleus of the infected cells. However, the mechanisms underlying such processes as the delivery of virus proteins to the nucleus and the export of progeny virus from the nucleus remain elusive. It is evident that nuclear transport signals should be involved in these processes. We performed an in silico search for the putative nuclear localization signal (NLS) and nuclear export signal (NES) motifs in the capsid proteins of the Blattella germanica Densovirus 1 (BgDV1) densovirus. A high probability NLS motif was found in the common C-terminal of capsid proteins together with a NES motif in the unique N-terminal of VP2. We also performed a global search for the nuclear traffic signals in the densoviruses belonging to five Densovirinae genera, which revealed high diversity in the patterns of NLSs and NESs. Using a heterologous system, the HeLa mammalian cell line expressing GFP-fused BgDV1 capsid proteins, we demonstrated that both signals are functionally active. We suggest that the NLS shared by all three BgDV1 capsid proteins drives the trafficking of the newly-synthesized proteins into the nucleus, while the NES may play a role in the export of the newly-assembled BgDV1 particles into the cytoplasm through nuclear pore complexes.
| S-EPMC6071259 | biostudies-literature
Project description:The role of receptor recognition in the emergence of virulent viruses was investigated in the infection of severe combined immunodeficient (SCID) mice by the apathogenic prototype strain of the parvovirus minute virus of mice (MVMp). Genetic analysis of isolated MVMp viral clones (n = 48) emerging in mice, including lethal variants, showed only one of three single changes (V325M, I362S, or K368R) in the common sequence of the two capsid proteins. As was found for the parental isolates, the constructed recombinant viruses harboring the I362S or the K368R single substitutions in the capsid sequence, or mutations at both sites, showed a large-plaque phenotype and lower avidity than the wild type for cells in the cytotoxic interaction with two permissive fibroblast cell lines in vitro and caused a lethal disease in SCID mice when inoculated by the natural oronasal route. Significantly, the productive adsorption of MVMp variants carrying any of the three mutations selected through parallel evolution in mice showed higher sensitivity to the treatment of cells by neuraminidase than that of the wild type, indicating a lower affinity of the viral particle for the sialic acid component of the receptor. Consistent with this, the X-ray crystal structure of the MVMp capsids soaked with sialic acid (N-acetyl neuraminic acid) showed the sugar allocated in the depression at the twofold axis of symmetry (termed the dimple), immediately adjacent to residues I362 and K368, which are located on the wall of the dimple, and approximately 22 A away from V325 in a threefold-related monomer. This is the first reported crystal structure identifying an infectious receptor attachment site on a parvovirus capsid. We conclude that the affinity of the interactions of sialic-acid-containing receptors with residues at or surrounding the dimple can evolutionarily regulate parvovirus pathogenicity and adaptation to new hosts.
| S-EPMC1346950 | biostudies-literature
Project description:The plant hormone jasmonic acid (JA) activates host defense responses against a broad spectrum of herbivores. Although it is well established that JA controls the expression of a large set of target genes in response to tissue damage, very few gene products have been shown to play a direct role in reducing herbivore performance. To test the hypothesis that JA-inducible proteins (JIPs) thwart attack by disrupting digestive processes in the insect gut, we used a MS-based approach to identify host proteins that accumulate in the midgut of Manduca sexta larvae reared on tomato (Solanum lycopersicum) plants. We show that two JIPs, arginase and threonine deaminase (TD), act in the M. sexta midgut to catabolize the essential amino acids Arg and Thr, respectively. Transgenic plants that overexpress arginase were more resistant to M. sexta larvae, and this effect was correlated with reduced levels of midgut Arg. We present evidence indicating that the ability of TD to degrade Thr in the midgut is enhanced by herbivore-induced proteolytic removal of the enzyme's C-terminal regulatory domain, which confers negative feedback regulation by isoleucine in planta. Our results demonstrate that the JA signaling pathway strongly influences the midgut protein content of phytophagous insects and support the hypothesis that catabolism of amino acids in the insect digestive tract by host enzymes plays a role in plant protection against herbivores.
| S-EPMC1323180 | biostudies-literature
Project description:European sea bass (Dicentrarchus labrax) is severely affected by nervous necrosis disease, caused by nervous necrosis virus (NNV). Two out of the four genotypes of this virus (red-spotted grouper nervous necrosis virus, RGNNV; and striped jack nervous necrosis virus, SJNNV) have been detected in sea bass, although showing different levels of virulence to this fish species. Thus, sea bass is highly susceptible to RGNNV, whereas outbreaks caused by SJNNV have not been reported in this fish species. The role of the capsid protein (Cp) amino acids 247 and 270 in the virulence of a RGNNV isolate to sea bass has been evaluated by the generation of recombinant RGNNV viruses harbouring SJNNV-type amino acids in the above mentioned positions (Mut247Dl965, Mut270Dl965 and Mut247 + 270Dl965). Viral in vitro and in vivo replication, virus virulence and fish immune response triggered by these viruses have been analysed. Mutated viruses replicated on E-11 cells, although showing some differences compared to the wild type virus, suggesting that the mutations can affect the viral cell recognition and entry. In vivo, fish mortality caused by mutated viruses was 75% lower, and viral replication in sea bass brain was altered compared to non-mutated virus. Regarding sea bass immune response, mutated viruses triggered a lower induction of IFN I system and inflammatory response-related genes. Furthermore, mutations caused changes in viral serological properties (especially the mutation in amino acid 270), inducing higher seroconversion and changing antigen recognition.
| S-EPMC6773868 | biostudies-other
Project description:A functional capsid protein (CP) is essential for host plant infection and insect transmission in monopartite geminiviruses. We studied two defective genomic DNAs of tomato yellow leaf curl virus (TYLCV), Sic and SicRcv. Sic, cloned from a field-infected tomato, was not infectious, whereas SicRcv, which spontaneously originated from Sic, was infectious but not whitefly transmissible. A single amino acid change in the CP was found to be responsible for restoring infectivity. When the amino acid sequences of the CPs of Sic and SicRcv were compared with that of a closely related wild-type virus (TYLCV-Sar), differences were found in the following positions: 129 (P in Sic and SicRcv, Q in Sar), 134 (Q in Sic and Sar, H in SicRcv) and 152 (E in Sic and SicRcv, D in Sar). We constructed TYLCV-Sar variants containing the eight possible amino acid combinations in those three positions and tested them for infectivity and transmissibility. QQD, QQE, QHD, and QHE had a wild-type phenotype, whereas PHD and PHE were infectious but nontransmissible. PQD and PQE mutants were not infectious; however, they replicated and accumulated CP, but not virions, in Nicotiana benthamiana leaf discs. The Q129P replacement is a nonconservative change, which may drastically alter the secondary structure of the CP and affect its ability to form the capsid. The additional Q134H change, however, appeared to compensate for the structural modification. Sequence comparisons among whitefly-transmitted geminiviruses in terms of the CP region studied showed that combinations other than QQD are present in several cases, but never with a P129.
| S-EPMC110531 | biostudies-literature
Project description:High enantiomeric excesses (ee's) of l-amino acids, including non-proteinogenic amino acid isovaline (Iva), were discovered in the Murchison meteorite, but the detailed molecular mechanism responsible for the observed ee of amino acids remains elusive and inconsistent, because Iva has an inverted circular dichroism (CD) spectrum with respect to α-H amino acids, e.g., alanine. To address this issue, we resort to accurate ab initio calculations for amino acids and their precursors in the Strecker synthesis. We evaluated their photolysis-induced ee in the range 5-11 eV including the Lyman alpha emission line (Lyα), the typical intensive 10.2 eV radiation ascribed to the early phase of galactic evolution. We show that only the aminonitrile precursors are characterized by positive ee in the Lyα region, explaining why right-handed circularly polarized Lyα (R-CP-Lyα) induces homologous l-amino acids. This study shows that the homochirality of amino acids is produced at the aminonitrile precursors stage.
| S-EPMC10084466 | biostudies-literature
Project description:Simple Summary Acheta domesticus (house cricket) flour is one of the most promising and sustainable sources of nutrients. It is rich in protein, minerals, fatty acids, amino acids, and vitamins and it has a low impact on the consumption of natural environmental resources. On the other side, fermentation with lactic acid bacteria represents a technological tool that can improve further the nutritional quality of flours. Therefore, the aim of the present research was to study the adaptability of the Lactobacillus plantarum strain on insect flour fermentation. Fatty acids, amino acids, minerals, and aroma volatile compounds were analyzed during 48 h of fermentation. Fermentation improved the nutritional quantity of the bioactive compounds, mainly after 24 h of fermentation, where they reached higher extended values. Overall, our findings indicate that insect flour is able to support the growth and development of the Lactobacillus plantarum strain, leading to an enriched insect flour sourdough that could be further used in the manufacturing of new products. Abstract Acheta domesticus (L.1758) has been recently accepted by the European Union as a novel food, being the third insect that has been approved for human consumption. Nowadays, researchers’ attention is focused on exploiting new protein sustainable sources, and, therefore, insect flour has gained more and more interest. Organic acids, fatty acids, amino acids, aroma volatile compounds, and minerals were analyzed through HPLC-RID (High-performance liquid chromatography), GC-MS (Gas chromatography-mass spectrometry), LC-MS (Liquid chromatography–mass spectrometry), ITEX/GC-MS and AAS (Atomic Absorption Spectrophotometry), respectively. Fermentation of the insect flour with Lactobacillus plantarum ATCC 8014 strain (Lp) leads to an increase in organic acids such as lactic, acetic, and oxalic, whilst citric acid decreases its value. SFA (saturated fatty acids) and MUFA (monosaturated fatty acids) groups were positively influenced by Lp fermentation; meanwhile, PUFA (polysaturated fatty acids) decreased during fermentation. A positive trend was observed for amino acids, aroma volatile content, and minerals enhancement during insect sourdough fermentation, mainly at 24 h of fermentation. Acheta domesticus (A. domesticus) sourdough fermentation represents a new tool that needs to be further exploited aiming to improve the nutritional qualities of the final products.
| S-EPMC9322958 | biostudies-literature
Project description:BackgroundPorcine circovirus type 2 (PCV2) is considered to be the primary causative agent of postweaning multisystemic wasting syndrome (PMWS), which has become a serious economic problem for the swine industry worldwide. The major genotypes, PCV2a and PCV2b, are highly prevalent in the pig population and are present worldwide. However, another newly emerging PCV2b genotype mutant, which has a mutation in its ORF2-encoded capsid protein, has been sporadically present in China, as well as in other countries. It is therefore important to determine the relative virulence of the newly emerging PCV2b genotype mutant, compared with the existing PCV2a and PCV2b genotypes, and to investigate whether the newly emerging mutant virus induces more severe illness.Methodology/principal findingsTwenty healthy, 30-day-old, commercial piglets served as controls or were challenged with PCV2a, PCV2b and the newly emerging mutant virus. A series of indexes representing different parameters were adopted to evaluate virulence, including clinical signs, serological detection, viral load and distribution, changes in immune cell subsets in the peripheral blood, and evaluation of pathological lesions. The newly emerging PCV2 mutant demonstrated more severe signs compatible with PMWS, characterized by wasting, coughing, dyspnea, diarrhea, rough hair-coat and depression. Moreover, the pathological lesions and viremia, as well as the viral loads in lymph nodes, tonsils and spleen, were significantly more severe (P<0.05) for piglets challenged with the newly emerging mutant compared with those in the groups challenged with PCV2a and PCV2b. In addition, a significantly lower average daily weight gain (P<0.05) was recorded in the group challenged with the newly emerging PCV2 mutant than in the groups challenged with the prevailing PCV2a and PCV2b.ConclusionsThis is believed to be the first report to confirm the enhanced virulence of the newly emerging PCV2 mutant in vivo.
| S-EPMC3400667 | biostudies-literature