35 results about "Uninfected cell" patented technology

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1LAI gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

The present invention provides a fusion protein construct (gp41HA) consisting of the ectodomain of the HIV-1IIIB envelope glycoprotein gp41 fused to a fragment of the influenza virus HA2 hemagglutinin protein. Immunization in-vivo via an intraperitoneal prime followed by intranasal or intragastric boosts with gp41HA induces high concentrations of serum IgG antibodies and fecal IgA antibodies that reacted with gp41 in HIV-1IIIB viral lysate and are cross-reactive with gp41 in HIV-1MN lysate. Followup analyses by indirect immunofluorescence showed that both serum IgG and fecal IgA recognized human peripheral blood mononuclear cells infected with either syncytium-inducing (SI) or non-syncytium-inducing (NSI) North American HIV-1 field isolates, but not uninfected cells.

Alterations of certain metabolite concentrations and fluxes that occur in response to viral infection are described. Host cell enzymes in the involved metabolic pathways are selected as targets for intervention; i.e., to restore metabolic flux to disadvantage viral replication, or to further derange metabolic flux resulting in “suicide” of viral-infected cells (but not uninfected cells) in order to limit viral propagation. While any of the enzymes in the relevant metabolic pathway can be selected, pivotal enzymes at key control points in these metabolic pathways are preferred as candidate antiviral drug targets. Inhibitors of these enzymes are used to reverse, or redirect, the effects of the viral infection. Drug candidates are tested for antiviral activity using screening assays in vitro and host cells, as well as in animal models. Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. The antiviral activity of enzyme inhibitors is demonstrated.

Fusion of the viral envelope, or infected cell membranes with uninfected cell membranes, is an essential step in the viral life cycle. Recent studies involving the human immunodeficiency virus type 1 (HIV-1) demonstrated that synthetic peptides (designated DP-107 and DP-178) derived from potential helical regions of the transmembrane (TM) protein, gp41, were potent inhibitors of viral fusion and infection. A computerized antiviral searching technology (C.A.S.T.) that detects related structural motifs (e.g., ALLMOTI5, 107x178x4, and PLZIP) in other viral proteins was employed to identify similar regions in the respiratory syncytial virus (RSV). Several conserved heptad repeat domains that are predicted to form coiled-coil structures with antiviral activity were identified in the RSV genome. Synthetic peptides of 16 to 39 amino acids derived from these regions were prepared and their antiviral activities assessed in a suitable in vitro screening assay. These peptides proved to be potent inhibitors of RSV fusion. Based upon their structural and functional equivalence to the known HIV-1 inhibitors DP-107 and DP-178, these peptides should provide a novel approach to the development of targeted therapies for the treatment of RSV infections.

The present invention is directed to the induction and characterization of a humoral immune response targeting “entry-relevant” gp41 structures. In its broadest aspect, the present invention is directed to methods of raising a neutralizing antibody response to a broad spectrum of HIV strains and isolates. The present invention targets particular molecular conformations or structures that occur at the cell surface of HIV during viral entry into host cells. Such a humoral response can be generated in vivo as a prophylactic measure in individuals to reduce or inhibit the ability of HIV to infect uninfected cells in the individual's body. Such a response can also be employed to raise antibodies against “entry relevant” gp41 structures. These antibodies can be employed for therapeutic uses, and as tools for further illuminating the mechanism of HIV cell entry.

The present invention provides methods and compositions useful for the elimination of latent HIV reservoirs that persist despite HAART. The methods and compositions overcome this latent barrier by inducing the replication of HIV in latently infected T cells while preventing the spread of the newly produced virions to uninfected cells by providing HAART simultaneously. Compositions of the invention comprise an activator of latent HIV expression, such as prostratin, and an inhibitor of histone deacetylase, such as TSA. A surprising finding of this invention is that the inhibitor of the histone deacetylase synergizes the effect of prostratin thus, allowing administering to a patient a lower, non-toxic dose of prostratin.

An assay for infection with one or more herpes simplex viruses that comprises a) dividing an antibody-containing serum sample into at least three serum subsamples, and b) separately incubating each with a physical matrix of cell antigens from i) uninfected cells, (ii) HSV-1-infected cells, or (iii) HSV-2-infected cells to form at least three serum subsample admixtures so that antibodies present in each admixture can immunoreact to form matrix-bound antibodies and at least three preadsorbed serum subsample portions. Each preadsorbed serum subsample portion is incubated with a mixture of matrix-bound antigens from cells uninfected by HSV-1 or HSV-2, infected by each of HSV-1 and by HSV-2 to permit antibodies to immunoreact with antigens present to form three matrix-bound immunoreactants. The amount of each immunoreaction is determined, and reaction amounts are prognostic for whether the subject whose serum was tested is infected by one, both, or neither of HSV-1 and HSV-2.

The present invention relates generally to a methodology for the isolation, purification and identification of peptide ligands presented by MHC positive cells. In particular, the methodology of the present invention relates to the isolation, purification and identification of these peptide ligands from soluble class I and class II MHC molecules which may be uninfected, infected, or tumorgenic. The methodology of the present invention broadly allows for these peptide ligands and their comcomittant source proteins thereof to be identified and used as markers for infected versus uninfected cells and / or tumorgenic versus nontumorgenic cells with said identification being useful for marking or targeting a cell for therapeutic treatment or priming the immune response against infected cells.

A method for modifying a wild strain of an entero-invasive Shigella to produce a modified strain of Shigella that can be used for making a vaccine against the wild strain of Shigella. The genome of the wild strain of Shigella is transformed so that it cannot substantially invade cells of a human host and cannot spread substantially within infected cells and from infected to uninfected cells of the host and cannot produce toxins which will kill substantial numbers of the host's infected, as well as uninfected, cells. A first gene of the wild strain of Shigella, coding for a protein necessary for the Shigella to invade cells of the host, and a second gene, coding for a protein necessary for the Shigella to spread within infected cells and between the infected and uninfected cells of the host, are mutagenized.

The invention relates to a preparation method of an artificial antibody, which is characterized by comprising the following steps: screening a target siRNA from a coronavirus conserved gene or a microsatellite, synthesizing a small hairpin shRNA with a loop ring from two complementary positive and negative siRNA chains, synthesizing ACE2 taking a receptor binding domain RBD as a ligand, respectively connecting the ACE2 to the positive and negative chains of the shRNA, synthesizing the artificial antibody formed by a shRNA region and an ACE2 region, and carrying out screening to obtain the artificial antibody. Wherein the bivalent ACE2 has the effects of neutralizing RBD and targeted delivery of shRNA, the shRNA is connected with a virus through the ACE2 and enters a target cell along with the infection of the virus, so that the side effect of non-specific delivery of the shRNA to an uninfected cell can be avoided, and the effects of anti-variant strains and neutralizing the virus by the ACE2 can be generated; in addition, an artificial antibody synthesized by two molecules of ACE2 and one molecule of shRNA and an immunologic adjuvant effect of shRNA enable ACE2 to have stronger antigenicity, and anti-ACE2 generated by stimulating an organism also has an antiviral effect.

An assay for infection with one or more herpes simplex viruses that comprises a) dividing an antibody-containing serum sample into at least three serum subsamples, and b) separately incubating each with a physical matrix of cell antigens from i) uninfected cells, (ii) HSV-1-infected cells, or (iii) HSV-2-infected cells to form at least three serum subsample admixtures so that antibodies present in each admixture can immunoreact to form matrix-bound antibodies and at least three preadsorbed serum subsample portions. Each preadsorbed serum subsample portion is incubated with a mixture of matrix-bound antigens from cells uninfected by HSV-1 or HSV-2, infected by each of HSV-1 and by HSV-2 to permit antibodies to immunoreact with antigens present to form three matrix-bound immunoreactants. The amount of each immunoreaction is determined, and reaction amounts are prognostic for whether the subject whose serum was tested is infected by one, both, or neither of HSV-1 and HSV-2.

The present invention relates generally to a methodology for the isolation, purification and identification of peptide ligands presented by MHC positive cells. In particular, the methodology of the present invention relates to the isolation, purification and identification of these peptide ligands from soluble class I and class II MHC molecules which may be from uninfected, infected, or tumorigenic cells. The methodology of the present invention broadly allows for these peptide ligands and their cognate source proteins thereof to be identified and used as markers for infected versus uninfected cells and / or tumorigenic versus nontumorigenic cells, with said identification being useful for marking or targeting a cell for therapeutic treatment or priming the immune response against infected / tumorigenic cells.