Abstract: Novel adeno-associated virus (AAV) isolates in nucleotide and amino acid forms and uses thereof are provided. The isolates show tropism for certain target tissues, such as blood stem cells, liver, heart and joint tissue, and may be used to transduce stem cells for introduction of genes of interest into the target tissues. Discrete modified portions of the cap gene, VP1, VP2, and VP3, may be used alone or in combination in the present methods.

Abstract: The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2 transfection experiments revealed that 2b/2a was genetically stable. Conclusion: The developed 2b/2a viruses provide a robust in vitro tool for research in HCV genotype 2b, including vaccine studies and functional analyses.

Abstract: The invention relates to recombinant MVA which is capable of expressing structural HCV antigens, functional parts of said structural antigens or epitopes of said structural antigens. The invention further relates to a pharmaceutical composition, especially in the form of a vaccine and containing the recombinant MVA according to the invention, to eukaryotic cells that contain the inventive recombinant MVA and to various uses of the recombinant MVA, for example for producing recombinant structural proteins, for producing a pharmaceutical preparation that is suitable for the therapy and prophylaxis of HCV infections and diseases thereby caused. The invention further relates to methods for producing recombinant MVA and recombinant structural HCV polypeptides encoded by said recombinant MVA, and to DNA or RNA of said recombinant MVA.

Abstract: Genotype 7a has been identified recently, thus not much is known about the biology of this new, major HCV genotype. The present inventors developed hepatitis C virus 7a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 7a strain QC69 and characterized them in Huh7.5 cells. Sequence analysis of 7a/JFH1 recombinants recovered after viral passage in Huh7.5 cells following 4 independent transfection experiments revealed adaptive mutations in Core, E2, NS2, NS5A and NS5B. In reverse genetic studies the importance of these mutations for improved growth kinetics was shown. Adapted 7a/JFH1 viruses showed growth kinetics, infectivity and RNA titers comparable to a previously developed 3a/JFH1 reference virus. Conclusion: The developed 7a/JFH1 viruses provide a robust in vitro tool for research in HCV genotype 7, including vaccine studies and functional analyses.

Abstract: The invention concerns polypeptides derived from the HIV-1 reverse transcriptase which are capable of inhibiting said polymerase and optionally also capable of inhibiting the HIV-1 integrase 3? processing activity, and their therapeutic applications.

Abstract: The invention relates to live attenuated VDV2 (VERO-Derived Vaccine Dengue serotype 2) strains which have been derived from the wild-type dengue-2 strain 16681 by passaging on PDK and Vero cells and nucleic acids thereof. The invention further relates to a vaccine composition which comprises a VDV2 strain.

Abstract: The invention relates to live attenuated VDV1 (VERO-Derived Dengue serotype 1 virus) strains which have been derived from the wild-type dengue-1 strain 16007 by passaging on PDK and sanitization on Vero cells and nucleic acids thereof. The invention further relates to a vaccine composition which comprises a VDV1 strain.

Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are antigens and/or their constituent epitopes confirmed to be recognized by T-cells derived from herpetic lesions or from uterine cervix. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

Abstract: An HCV/GBV-B chimeric virus which maintains the replication function of HCV and is capable of infecting tamarin is disclosed in order to construct an HCV animal model which can be used as a development or evaluation system for therapeutic agents for HCV. The HCV/GBV-B chimeric RNA comprises an RNA of hepatitis C virus and an RNA of GB virus-B, wherein the RNA of hepatitis C virus comprises an RNA encoding leucine at the 1804th position and lysine at the 1966th position in the amino acid sequence of the polyprotein of hepatitis C virus.

Abstract: The invention features polypeptide and polynucleotide sequences based on the 134R sequence. In some embodiments, these sequences include a heterologous signal sequence, such as the myxoma virus T7 signal sequence. The invention also features methods for treating immunological disorders and neoplasms (e.g., cancer) using the polypeptides and nucleotides described herein. Finally, the invention features fusion proteins including the myxoma virus T7 signal sequence.

Abstract: The present invention relates to a novel form of core+1 protein of Hepatitis C virus (HCV), designated shorter form core+1 protein. The shorter form core+1 protein of Hepatitis C virus is the product of translation of a coding sequence consisting of all or part of a nucleotide sequence extending from nucleotide 598 to nucleotide 920 within the core+1 ORF of HCV represented on FIG. 3B. The invention also provides methods for detecting infection by Hepatitis C virus in biological samples, methods of screening compounds which interact with viral propagation in HCV infected cells or screening of compounds impaction on the expression of shorter form core+1 protein and uses of these compounds for the preparation of compositions useful for their anti-viral activities.

Abstract: This disclosure provides modified cytosine deaminases (CDs). The disclosure further relates to cells and vector expressing or comprising such modified CDs and methods of using such modified CDs in the treatment of disease and disorders.

Abstract: The present invention relates to the discovery that Tat polypeptides may be used as immunoregulators to enhance the immune response to infectious diseases. More particularly, Tat polypeptides may be used as immunoregulators to enhance immune responses to microbial infections, for example, viral and bacterial infections. In accordance with the present invention, Tat polypeptides interact with CCR3 to stimulate platelet activation. The novel finding of the present inventors, therefore, presents new applications for which Tat nucleic and amino acid sequences, and compositions thereof may be used to advantage. Applications for which the Tat nucleic and amino acid sequences and compositions thereof of the invention may be used include, but are not limited to, various research and therapeutic applications as described herein. Also provided is a kit comprising Tat nucleic and/or amino acid sequences, Tat activity compatible buffers, and instruction materials.

Abstract: The invention relates to a recombinant classical swine fever virus (CSFV). A preferred recombinant CSFV comprises a deletion of at least one amino acid in a “TAVSPTTLR” domain of the E2 protein. The invention further relates to a vaccine comprising the recombinant CSFV, a method for generating a recombinant CSFV, and use of a recombinant CSFV.

Abstract: The present invention refers to a recombinant koi herpesvirus (KHV) or Cyprinid herpesvirus 3 (CyHV-3), which is immunogenic in fish, preferably in carps, more preferably in Cyprinus carpio, and to a vaccine for preventive and/or therapeutic treatment of a disease caused by koi herpesvirus (KHV) or CyHV-3. The 5 recombinant herpesvirus is used to confer immunity on fish, preferably on carps, more preferably on Cyprinus carpio, against a disease caused by koi herpesvirus (KHV) or Cyprinid herpesvirus 3 (CyHV-3).

Abstract: NS4B is one of the non-structural proteins of classical swine fever virus. By using functional genetics, we have discovered, in the predicted amino acid sequence of NS4B of CSFV strain Brescia, a motif that resembles those found in the toll-like receptor (TLR) proteins, a group of host cell proteins involved in the development of anti-viral mechanisms. We have located the TLR motif in two groups of amino acid triplets at amino acid positions 2531-3 (residues IYK) and 2566-8 (residues VGI) of the CSFV NS4B glycoprotein. We have constructed a recombinant CSFV (derived from an infectious clone containing the genetic information of the highly virulent strain Brescia) containing amino acid substitutions in the three amino acid residues at positions 2566, 2567 and 2568, where the VGI triplet has been replaced by an AAA triplet inside the NS4B glycoprotein. The obtained virus, named NS4B-VGIv, was completely attenuated in swine, showing a limited ability in spreading during the infection in vivo.

Abstract: The present invention relates to nucleic acid molecules found in the genome of the Citrus Leprosis Virus (CiLV), which is associated to Citrus Leprosis (CiL) disease. The cloned CiLV nucleic acid molecules can be used as probes or can be used to design oligonucleotide primers useful in assays, such as a polymerase chain reaction, for detecting the presence of CiLV in biological samples, particularly leaves, roots and other tissues or organs of plants, such as plants from the genera Citrus and Poncirus. The invention comprises introducing the mentioned nucleic acid molecules in cloning vectors and cloning the recombinant nucleic acid molecules in cells, such as prokaryotes (e.g., bacteria like E. coli), and eukaryotes (e.g., yeast, COS, CHO, and other cells). The cloned CiLV nucleic acid molecules are expressed in cells to provide immunogenic proteins which can be used to raise antibodies against the CiLV, which can then be used to detect the presence of the CiLV virus in biological samples.

Abstract: The present invention provides a novel chimeric porcine circovirus infectious DNA clone and live attenuated chimeric virus with the PCV2, preferably of subtype PCV2b, capsid gene integrated into a non-pathogenic PCV1 virus genome. In a particular embodiment, the PCV2 capids gene is of subtype PCV2b, the predominant subtype circulating in pigs worldwide. The attenuated chimeric virus, designated PCV1-2b, effectively protects pigs from PCV2b challenges, and can be used as a live vaccine, as well as an inactivated (killed) vaccine, that provides protection and cross protection against PCV2b and PCV2a subtypes infection. The live attenuated vaccine of the present invention is also effective protecting pigs from porcine circovirus-associated disease (PCVAD).

Abstract: The present invention relates to Human Immunodeficiency Virus-1 (HIV-1) Group P of the strain designated 06CMU14788 and fragments thereof, primers which are derived from HIV-1 Group P, immunogenic regions thereof, immunoassays and nucleic acid based assays for the detection of Human Immunodeficiency Virus (HIV) that employ said HIV-1 Group P or fragments thereof and therapeutic compositions containing said HIV-1 Group P or fragments thereof.

Abstract: The present invention provides human binding molecules specifically binding to a host cell protein and having virus neutralizing activity, nucleic acid molecules encoding the human binding molecules, compositions comprising the human binding molecules and methods of identifying or producing the human binding molecules. The human binding molecules can be used in the diagnosis, prophylaxis and/or treatment of viral infections.

Abstract: Bacterial packaging strains useful for generating recombinant double-stranded RNA nucleocapsids (rdsRNs) are provided. The packaging strains are useful for the production of RNA encoding vaccine antigens, bioactive proteins, immunoregulatory proteins, antisense RNAs, and catalytic RNAs in eukaryotic cells or tissues. Recombinant ssRNA is introduced into the strains and packaged to form rdsRNs de novo.

Abstract: Methods and compositions for producing targeted delivery vectors are provided. Such vectors are useful for treating neoplastic disorders. Also provided are protocols for administering targeted delivery vectors in a clinical setting such that a therapeutic effect is achieved.

Abstract: Provided are methods and means to increase the stability and/or the packaging capacity of recombinant adenoviruses, by overexpression of pIX in an adenoviral packaging cell, by retaining at least a part of the E1B-55K region in the recombinant adenoviral vector or by regulating pIX with a heterologous promoter. The invention further relates to methods and means for the production of such adenoviruses on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenovirus and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products in the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.

Abstract: A method of controlling a genetically-modified plant, comprising (a) providing a genetically-modified plant, whereby cells of said genetically-modified plant contain a heterologous nucleic acid and whereby said genetically-modified plant is inactive with regard to a cellular process of interest, (b) switching on said cellular process of interest by directly introducing a polypeptide from a cell-free composition into cells containing said heterologous nucleic acid wherein said polypeptide and said heterologous nucleic acid are mutually adapted such that said polypeptide is capable of switching on said cellular process of interest.

Abstract: Disclosed are compositions and methods for preventing or reducing harm resulting from pathogen infection. For example, disclosed are peptides that inhibit the processing of toxins normally cleaved by proprotein convertase enzymes.

Abstract: Embodiments of the present invention include conserved-element vaccines and methods for designing and producing conserved-element vaccines. A conserved-element vaccine (“CEVac”) is a recombinant and/or synthetic vaccine that incorporates only highly conserved epitopes from an observed set of pathogen variants. The conserved epitopes are identified computationally by aligning biopolymer sequences, such as concatenated polypeptide sequences that together represent a pathogen proteome, corresponding to an observed set of pathogen variants, and computationally selecting conserved subsequences according to a number of subsequence-selection criteria.

Abstract: The present invention aims to express influenza virus RNA polymerase on a large scale, to crystallize the influenza virus RNA polymerase, and to provide a method for screening a substance capable of serving as an active ingredient in anti-influenza drugs. The present invention provides a complex comprising a polypeptide consisting of an amino acid sequence at positions 678-757 of the RNA polymerase PB1 subunit in influenza A/Puerto Rico/8/34 H1N1 and a polypeptide consisting of an amino acid sequence at positions 1-37 of RNA polymerase PB2 subunit in influenza A/Puerto Rico/8/34 H1N1. This complex can be crystallized in the presence of a precipitant such as potassium phosphate and PEG4000. Moreover, with the use of information on the crystal structure of this complex, it is possible to provide a method for screening a substance capable of serving as an active ingredient in anti-influenza drugs.

Abstract: Various tetrahydropyrazolo[1,5-a]pyrimidine compounds, compositions, methods of making, and methods for the prevention and treatment of HCV infections and associated diseases are disclosed. The invention further relates to biomarkers for identification of HCV strains which are resistant to the tetrahydropyrazolo[1,5-a]pyrimidine compounds.

Abstract: The invention provides polynucleotides and polypeptides encoded therefrom that are capable of inducing immune responses to a human immunodeficiency virus. Compositions and methods for utilizing polynucleotides and polypeptides of the invention are also provided.

Abstract: Aspects of the present invention relate to isolated nucleic acids that encode a consensus DIII domain of protein E and vaccines made using same, and also methods for using the aforementioned to generate in a host an immune response against multiple serotypes of flavivirus, particularly West Nile virus and Japanese encephalitis virus.

Abstract: Compositions and methods for protection against bacterial contamination are disclosed Antibacterial proteins and methods of use thereof are also disclosed

Abstract: Adeno-associated virus 7 sequences, vectors containing same, and methods of use are provided.

Abstract: The present invention discloses a codon-optimized gene encoding major capsid protein L1 of human papilloma virus, which is capable, after transduced into a yeast cell, of efficiently expressing the major capsid protein L1 of human papilloma virus. The present invention also discloses an immunogenic macromolecule which is essentially produced by expression of said codon-optimized gene encoding the major capsid protein L1 of human papilloma virus in a yeast cell. The present invention further discloses the use of said immunogenic macromolecule and a composition comprising said immunogenic macromolecule.

Abstract: A polypeptide comprising a preS1 region of hepatitis B virus (HBV), or a fragment thereof, and/or the preS2 region of HBV or a fragment thereof, and methods of use to inhibit virus infection are disclosed. A lentivirus comprising hepatitis B virus (HBV) envelope proteins, or a fragment thereof, and/or the L envelope protein of HBV and/or the M envelope protein of HBV or a fragment thereof, and/or the S envelope protein of HBV or a fragment thereof, and methods of use of this lentivirus HBV pseudovirus as a gene therapy to target hepatocytes for the administration of therapeutic agents are also disclosed.

Abstract: The present invention relates to a novel RNA picornavirus that is called Seneca Valley virus (“SVV”). The invention provides isolated SVV nucleic acids and proteins encoded by these nucleic acids. Further, the invention provides antibodies that are raised against the SVV proteins. Because SVV has the ability to selectively kill some types of tumors, the invention provides methods of using SVV and SVV polypeptides to treat cancer. Because SVV specifically targets certain tumors, the invention provides methods of using SVV nucleic acids and proteins to detect cancer. Additionally, due to the information provided by the tumor-specific mechanisms of SVV, the invention provides methods of making new oncolytic virus derivatives and of altering viruses to have tumor-specific tropisms.

Abstract: Transgenic plants with increased resistance to geminivirus infection, and nucleic acid constructs useful in producing such plants, are described. In addition, methods of making the transgenic plants of the present invention are included. The transgenic plants express a mutant AL1/C1 geminivirus protein, which increases resistance to infection by at least one geminivirus, compared to a non-transformed control plant.

Abstract: The present invention provides a method for generating negative-stranded segmented RNA viruses using linear expression constructs in the presence of helper virus.

Abstract: The present invention relates to non-replicative recombinant retrovirus packaging cells able to grow in suspension in a serum-free medium. In particular, the present invention relates to a human embryonic 293SF-based cell line stably expressing gag and pol gene products from the murine Moloney leukemia virus (MLV) and either the feline RD114 env gene, the gibbon ape leukemia virus (GLV) env gene, or the amphotropic 4070Aenv gene. This particular combination allows the production of high titer of non-replicative retrovirus pseudotyped and prevents the recombination of plasmids. The recombinant retroviruses produced from these cells are safer and easier to produce for clinical use in gene therapy.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transfering heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication competent helper virus.

Abstract: This invention provides a new approach to the design of a virus with a defective replication cycle, which can be rescued by wild type virus co-infection, and which expresses foreign antigenic epitopes that contribute to the elimination of virus infected cells and then to viral clearance. The vector of the invention, by expression of epitopes derived from common pathogens, by-passes existing tolerance of virus specific T cell responses. The vector will only replicate in virus infected cells.

Abstract: This disclosure is directed, inter alia, to polynucleotides, polypeptides, vectors, cells and compositions comprising the same, and their use in affecting viral pathogenesis, in particular for influenza viral infection.

Abstract: The present invention relates to a method to introduce a nucleic acid molecule into a felid by administration of a nucleic acid-cationic lipid complex composition. The method includes the step of administering to the felid, by a parenteral route, a nucleic acid-cationic lipid complex to elicit and/or enhance an immune response. In one embodiment, this method enhances the immune response in a felid compared to a method in which a naked DNA vaccine is administered to a felid. Also provided is a method to deliver a nucleic acid to a felid. This method comprises parenterally administering to the felid a composition that includes a nucleic acid molecule complexed with a cationic lipid.

Abstract: Methods and compositions concerning mutant flaviviruses with host range mutations. In some embodiments the invention concerns nucleotide sequences that encode mutant flavivirus proteins. Viruses comprising these sequences that display reduced replication in mammalian cells are provided. In further aspects of the invention, flavivirus vaccine compositions are provided. In another embodiment the invention provides methods for vaccination against flavivirus infection.

Abstract: The present invention relates to a method of detecting the presence or absence of herpes simplex virus (HSV) in a sample based on amplifying a portion of the Glycoprotein G(US4) gene of HSV and detecting the presence of the amplified nucleic acid using primers and detector primers as described herewith. The method of the invention further identifies the type of HSV, either HSV-1 or HSV-2, in a sample. Also encompassed by the invention is a kit comprising the primers and detector primers which may be used with the amplification method described herewith.

Abstract: The present invention includes polypeptides, polynucleotides, antibodies, and vaccines associated with Runting Stunting Syndrome (RSS) in poultry. The present invention also includes diagnostic methods based on such polypeptides, polynucleotides, and antibodies and methods of protecting poultry, including chickens, against RSS by the administration of such polypeptides, polynucleotides, antibodies, and vaccines.

Abstract: The invention concerns nucleotides vaccines encoding influenza proteins with few or no glycosylation sites. Since these first introductions of pandemic influenzas the viruses have drifted, accumulating mutations at antigenic sites, but also the N-glycosylation pattern has changed during the drifted years, accumulating N-linked glycosylation sequons that help mask the antigenic sites for recognition by the host immune system. These “naked” initial haemagglutinins induce a broad cross reactivity against widely drifted influenza subtypes. The origin of the DNA or RNA can be both pandemic influenza strains, which codes for proteins which have a naturally low content of glycosylation sites and/or DNA or RNA from non-pandemic influenza strains where the nucleotides have been mutated or changed so it encodes for proteins with less or no glycosylation sites. The invention also discloses DNA or RNA encoding the haemagglutinin (HA) from pandemic influenza A, e.g.

Abstract: Anti-peptide monoclonal antibodies (MAb's) specific for Exotic Newcastle Disease (END) are used for rapid diagnostic identification between poultry infected with vaccine strains of NDV (LaSota/B1) and END virus (ENDV). Exotic Newcastle Disease is a contagious and fatal viral disease of birds and poultry. The present invention provides for diagnostic detection of ENDV in commercial poultry.

Abstract: The present invention relates to a gene derived from a novel fulminant hepatitis C virus strain, an HCV replicon RNA with a high replication efficiency obtained using the gene, and an HCV replicon-replicating cell transfected with the replicon RNA. When the HCV replicon RNA and the HCV replicon-replicating cell of the present invention are used, HCV proteins can be continuously produced in a large amount.

Abstract: This invention relates to soluble forms of F glycoprotein from Hendra and Nipah virus and to compositions comprising soluble forms of F glycoprotein from Hendra and Nipah virus. This invention further relates to soluble oligomers of F glycoprotein from Hendra and Nipah virus. This invention also relates to nucleic acids encoding soluble forms of F glycoprotein from Hendra and Nipah virus. This invention also relates to diagnostic and therapeutic methods using the soluble forms of F glycoprotein from Hendra and Nipah virus. Further, this invention relates to antibodies, including neutralizing antibodies, and to vaccines for the prevention, diagnosis and treatment of infection by Hendra and Nipah viruses.

Abstract: A recombinant vector comprises simian adenovirus 43, 45, 46, 47, 48, 49 or 50 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus 43, 45, 46, 47, 48, 49 or 50 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.