The disclosure provides compositions and methods involving viral RNA segments for use in modulating immune responses, including inhibition inflammation related to pathogenic T-cell activation. In addition, modification of the viral sequences responsible for modulating immune response provides for improved vaccine formulations.

The present invention pertains to a non-human genetically modified animal with increased susceptibility to infection with a human virus. The invention suggests to genetically impair the expression of newly identified viral infection repression factors CD302, Cr11, Ndufc2, AW112010, Scarb2 and Zc3hav1, which markedly improves infection with human viruses in none-human hosts. Furthermore provided are methods for the generation of the animal of the invention, methods for increasing or reducing the susceptibility of a cell to viral infection, methods for screening novel modulators of viral infection as well as new therapy options for the treatment of viral diseases, in particular hepatitis C.

The application relates to methods of treating chronic viral infection by modulating Tim-3 activity. In addition, the present application relates to methods of diagnosing or monitoring immune system activity or function, chronic viral infection and inflammatory disease using Tim-3 expression.

Hepatitis C virus (HCV) infection is a leading cause for liver cirrhosis and hepatocellular carcinoma worldwide.sup.2. Current therapeutic regimens are usually poorly tolerated and only effective in a proportion of infected individuals. We discovered a peptide with sequence of DEAQETAVSSHEQD (SEQ ID NO: 1), a fragment of rabbit α1-antiproteinase F, and its derivatives DEAQETAVSSHEQ (SEQ ID NO: 2) and QETAVSSHEQD (SEQ ID NO: 3), significantly inhibit serum-borne HCV replication in hADSC and human hepatocytes.

The present invention relates to immuno-protected encapsulated cells producing an immunomodulator, for example GM-CSF (granulocyte-macrophage colony stimulating factor). The cells of the invention are particularly well adapted for providing an active adjuvant or immunomodulator, for example in the context of immunization in humans and animals. These cells can be used for vaccination where they provide the immunomodulator in an active form, in a continuous, non-immunogenic manner in the immediate vicinity of the vaccine antigen(s). The invention also relates to a vaccine composition comprising immuno-protected encapsulated cells producing an immunomodulator and an antigenic component. The invention also relates to a kit comprising a cell as described and an antigenic component. The strategy of the invention is perfectly suited for both cancer immunotherapy and vaccination against infectious agents.

Disclosed herein are methods for producing virus-infected cell lines or animal models, wherein an enveloped virus including a lipid bilayer is mixed with a bile acid or a bile acid derivative, which allows the lipid bilayer to be replaced with a lipid bilayer derived from a target animal. Also disclosed herein are the virus-infected cell lines or animal models so produced and methods of screening a therapeutic candidate for a viral disease using the same.

PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.

The present invention pertains to a non-human genetically modified animal with increased susceptibility to infection with a human virus. The invention suggests to genetically impair the expression of newly identified viral infection repression factors CD302, Cr11, Ndufc2, AW112010, Scarb2 and Zc3hav1, which markedly improves infection with human viruses in none-human hosts. Furthermore provided are methods for the generation of the animal of the invention, methods for increasing or reducing the susceptibility of a cell to viral infection, methods for screening novel modulators of viral infection as well as new therapy options for the treatment of viral diseases, in particular hepatitis C.

The present disclosure provides rapid and non-invasive methods for determining whether a patient will benefit from treatment with therapeutic agents that inhibit Hepatitis C virus (HCV). These methods are based on detecting HCV RNA and/or anti-HCV antibodies in small-volume dried biological fluid samples that are collected using a microsampling device. Kits for use in practicing the methods are also provided.

PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.