Analysis of the Genome of the Sexually Transmitted Insect Virus Helicoverpa zea Nudivirus 2

The sexually transmitted insect virus Helicoverpa zea nudivirus 2 (HzNV-2) was determined to have a circular double-stranded DNA genome of 231,621 bp coding for an estimated 113 open reading frames (ORFs). HzNV-2 is most closely related to the nudiviruses, a sister group of the insect baculoviruses. Several putative ORFs that share homology with the baculovirus core genes were identified in the viral genome. However, HzNV-2 lacks several key genetic features of baculoviruses including the late transcriptional regulation factor, LEF-1 and the palindromic hrs, which serve as origins of replication. The HzNV-2 genome was found to code for three ORFs that had significant sequence homology to cellular genes which are not generally found in viral genomes. These included a presumed juvenile hormone esterase gene, a gene coding for a putative zinc-dependent matrix metalloprotease, and a major facilitator superfamily protein gene; all of which are believed to play a role in the cellular proliferation and the tissue hypertrophy observed in the malformation of reproductive organs observed in HzNV-2 infected corn earworm moths, Helicoverpa zea

The Genome of Camelpox Virus

AbstractCamelpox virus (CMLV), a member of the Orthopoxvirus genus in the Poxviridae, is the etiologic agent of a disease of camels. Here we report the CMLV genomic sequence with analysis. The 205,719-bp CMLV genome contains 211 putative genes and consists of a central region bound by identical inverted terminal repeats of approximately 7 kb. A high degree of similarity in gene order, gene content, and amino acid composition in the region located between CMLV017 and CMLV184 (average 96% amino acid identity to vaccinia virus (VACV)) indicates a close structural and functional relationship between CMLV and other known orthopoxviruses (OPVs). Notably, CMLV contains a unique region of approximately 3 kb, which encodes three ORFs (CMLV185, CMLV186, CMLV187) absent in other OPVs. These ORFs are most similar to B22R homologues found in other chordopoxvirus genera. Among OPVs, CMLV is the most closely related to variola virus (VARV), sharing all genes involved in basic replicative functions and the majority of genes involved in other host-related functions. Differences between CMLV and VARV include deletion and disruption of a large number of genes. Twenty-seven CMLV ORFs are absent in VARV, including seven full-length homologues of NMDA-like receptor, phospholipase D, Schlafen, MT-4 virulence, kelch, VACV C8L, and cowpox (CPXV) B21R proteins. Thirty-eight CMLV ORFs, some of which are fragments of larger genes, differ in size from corresponding VARV ORFs by more than 10% (amino acids). Genome structure and phylogenetic analysis of DNA sequences for all ORFs indicate that CMLV is clearly distinct from VARV and VACV and, as it has been suggested for VARV, it may have originated from a CPXV virus-like ancestor

Identification of T-cell epitopes in African swine fever virus CD2v and C-type lectin proteins.

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available, and progress is hindered by lack of knowledge concerning the extent of ASF virus (ASFV) strain diversity and the viral antigens conferring type-specific protective immunity in pigs. Previously, we demonstrated that ASFV serotype-specific proteins CD2v (EP402R) and/or C-type lectin (EP153R) are important for protection against homologous ASF infection. Here, we identified six discrete T-cell epitope regions present on CD2v and C-type lectin using IFN-γ ELISpot assay and PBMCs from ASF immune animals, indicating cellular reactivity to these proteins in the context of ASFV infection and protective immunity. Notably, three of the epitope regions map to previously described serotype-specific signature regions of these proteins. Improved understanding of ASFV protective antigens, relevant epitopes and their diversity in nature will facilitate ASFV subunit vaccine design and development

Vaccinia virus gene F3L encodes an intracellular protein that affects the innate immune response

The Vaccinia virus BTB/kelch protein F3 has been characterized and its effects on virus replication in vitro and virus virulence in vivo have been determined. The loss of the F3L gene had no effect on virus growth, plaque phenotype or cytopathic effect in cell culture under the conditions tested. However, the virulence of a virus lacking F3L in an intradermal model was reduced compared with controls, and this was demonstrated by a significantly smaller lesion and alterations to the innate immune response to infection. The predicted molecular mass of the F3 protein is 56 kDa; however, immunoblotting of infected cell lysates using an antibody directed against recombinant F3 revealed two proteins of estimated sizes 37 and 25 kDa

Brazilian Vaccinia Viruses and Their Origins

Genetic diversity enables this virus to persist in Brazil and other parts of the world

Análise de vida à fadiga sob carregamentos não proporcionais através de modelo de dano contínuo

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Mecânica, 2016.Neste trabalho, busca-se utilizar o modelo de dano contínuo de Lemaitre como uma ferramenta de obtenção de vida em fadiga multiaxial para carregamentos proporcionais e não proporcionais. Primeiramente é apresentado o modelo matemático de Lemaitre, em que são formuladas as relações constitutivas necessárias à elaboração do modelo. O modelo de Chaboche foi escolhido para descrever a lei de evolução da tensão de endurecimento cinemático. Em seguida, é desenvolvido o modelo numérico para a solução das equações constitutivas, utilizando a lei de Chaboche com três termos e discretização implícita de Euler. Após, é feita a identificação dos parâmetros constitutivos do modelo para os aços 304 e S460N e para a liga de alumínio 6061-T6. É feita a implementação do modelo em uma rotina em linguagem FORTRAN, a qual é submetida a carregamentos uniaxiais e multiaxiais proporcionais e não proporcionais para cada material. Os dados de vida em fadiga obtidos pelo modelo de Lemaitre são, então, comparados com os dados experimentais disponíveis na literatura. É feita, em seguida, uma análise das amplitudes de tensão obtidas pelo modelo, as quais são comparadas com os dados experimentais. São obtidas, também, curvas de evolução do dano para cada carregamento e material. Os resultados obtidos mostram que o modelo de dano de Lemaitre descreve de maneira adequada o comportamento dos materiais analisados em fadiga de baixo ciclo, quando altas amplitudes de deformação são aplicadas.This project seeks to use Lemaitre’s Continuous Damage Model to obtain fatigue life estimates under multiaxial proportional and non-proportional loadings. Initially, the Lemaitre’s mathematical model is presented, by formulating the necessary constitutive relations. Chaboche’s model was chosen to describe the kinematic hardening law. Then, the numerical model necessary to solve the constitutive relations is developed, utilizing the Chaboche’s law with 3 terms and Euler’s implicit discretization. Then, the material parameters are identified for 304 and S460N steels and 6061-T6 aluminum alloy. The model is implemented in a FORTRAN routine, which is submitted to uniaxial and proportional and non-proportional multiaxial loading histories. The fatigue life data obtained from Lemaitre’s damage model is compared to experimental data. Then, a stress amplitude analysis is conducted and the numerical stresses are compared to experimental data. Damage evolution curves are also obtained for each material and loading. The results show that Lemaitre’s damage model describes adequately the behavior of the analyzed materials under low cycle fatigue, when low strain amplitudes are being applied to the specimen

Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein

Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators of innate immune signalling. VACV protein N1 is an intracellular homodimer that contributes to virus virulence and was reported to inhibit nuclear factor (NF)-κB signalling. However, analysis of NF-κB signalling in cells infected with recombinant viruses with or without the N1L gene showed no difference in NF-κB-dependent gene expression. Given that N1 promotes virus virulence, other possible functions of N1 were investigated and this revealed that N1 is an inhibitor of apoptosis in cells transfected with the N1L gene and in the context of VACV infection. In support of this finding virally expressed N1 co-precipitated with endogenous pro-apoptotic Bcl-2 proteins Bid, Bad and Bax as well as with Bad and Bax expressed by transfection. In addition, the crystal structure of N1 was solved to 2.9 Å resolution (0.29 nm). Remarkably, although N1 shows no sequence similarity to cellular proteins, its three-dimensional structure closely resembles Bcl-xL and other members of the Bcl-2 protein family. The structure also reveals that N1 has a constitutively open surface groove similar to the grooves of other anti-apoptotic Bcl-2 proteins, which bind the BH3 motifs of pro-apoptotic Bcl-2 family members. Molecular modelling of BH3 peptides into the N1 surface groove, together with analysis of their physico-chemical properties, suggests a mechanism for the specificity of peptide recognition. This study illustrates the importance of the evolutionary conservation of structure, rather than sequence, in protein function and reveals a novel anti-apoptotic protein from orthopoxviruses

Widespread Horizontal Gene Transfer from Circular Single-stranded DNA Viruses to Eukaryotic Genomes

<p>Abstract</p> <p>Background</p> <p>In addition to vertical transmission, organisms can also acquire genes from other distantly related species or from their extra-chromosomal elements (plasmids and viruses) via horizontal gene transfer (HGT). It has been suggested that phages represent substantial forces in prokaryotic evolution. In eukaryotes, retroviruses, which can integrate into host genome as an obligate step in their replication strategy, comprise approximately 8% of the human genome. Unlike retroviruses, few members of other virus families are known to transfer genes to host genomes.</p> <p>Results</p> <p>Here we performed a systematic search for sequences related to circular single-stranded DNA (ssDNA) viruses in publicly available eukaryotic genome databases followed by comprehensive phylogenetic analysis. We conclude that the replication initiation protein (Rep)-related sequences of geminiviruses, nanoviruses and circoviruses have been frequently transferred to a broad range of eukaryotic species, including plants, fungi, animals and protists. Some of the transferred viral genes were conserved and expressed, suggesting that these genes have been coopted to assume cellular functions in the host genomes. We also identified geminivirus-like and parvovirus-like transposable elements in genomes of fungi and lower animals, respectively, and thereby provide direct evidence that eukaryotic transposons could derive from ssDNA viruses.</p> <p>Conclusions</p> <p>Our discovery extends the host range of circular ssDNA viruses and sheds light on the origin and evolution of these viruses. It also suggests that ssDNA viruses act as an unforeseen source of genetic innovation in their hosts.</p

Hormone Therapy and the Risk of Breast Cancer in BRCA1 Mutation Carriers

Background: Hormone therapy (HT) is commonly given to women to alleviate the climacteric symptoms associated with menopause. There is concern that this treatment may increase the risk of breast cancer. The potential association of HT and breast cancer risk is of particular interest to women who carry a mutation in BRCA1 because they face a high lifetime risk of breast cancer and because many of these women take HT after undergoing prophylactic surgical oophorectomy at a young age. Methods: We conducted a matched case-control study of 472 postmenopausal women with a BRCA1 mutation to examine whether or not the use of HT is associated with subsequent risk of breast cancer. Breast cancer case patients and control subjects were matched with respect to age, age at menopause, and type of menopause (surgical or natural). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with conditional logistic regression. Statistical tests were two-sided. Results: In this group of BRCA1 mutation carriers, the adjusted OR for breast cancer associated with ever use of HT compared with never use was 0.58 (95% CI = 0.35 to 0.96; P =. 03). In analyses by type of HT, an inverse association with breast cancer risk was observed with use of estrogen only (OR = 0.51, 95% CI = 0.27 to 0.98; P =. 04); the association with use of estrogen plus progesterone was not statistically significant (OR = 0.66, 95% CI = 0.34 to 1.27; P =. 21). Conclusion: Among postmenopausal women with a BRCA1 mutation, HT use was not associated with increased risk of breast cancer; indeed, in this population, it was associated with a decreased risk