Diagnosis and treatment of viral diseases
Provided are methods of diagnosing a viral disease such as idiopathic pulmonary fibrosis, Castleman's disease, a lymphoma, a thymoma or a sarcoma in a patient by identifying one or more virus-specific elements such as a nucleic acid or a viral protein or a patient antibody to a virus-specific element, as well as to kits for diagnosing the viral disease in a patient. Further provided are methods of monitoring disease progression and/or the efficacy of therapy by measuring the levels of a virus-specific element in a sample from a patient, and methods of identifying therapeutic agents that show efficacy in reducing levels of virus-specific agents in vitro. Still further provided are methods of treating idiopathic pulmonary fibrosis, a lymphoproliferative disease and cancer, as well as to methods of preventing viral infection, including Herpesvirus saimiri infection.
1. A method of diagnosing and treating idiopathic pulmonary fibrosis in a human patient comprising the steps of:
(a) providing
(i) a clinical sample of a human patient comprising lung tissue or a bronchial lavage, and
(ii) monoclonal antibodies to at least two Herpesvirus saimiri protein targets selected from the group consisting of viral DHFR, viral cyclin D, viral IL-17 and viral thymidylate synthase, wherein the at least two monoclonal antibodies are specific to said Herpesvirus saimiri protein targets versus their human analogs;
(b) contacting said clinical sample (i) with said monoclonal antibodies (ii);
(c) allowing binding to take place between said monoclonal antibodies (ii) and said protein targets of the antibodies in said clinical sample (i) if present;
(d) detecting binding of said monoclonal antibodies (ii) to said protein targets in said clinical sample (i), thereby providing a diagnosis of said human patient as having idiopathic pulmonary fibrosis; and
(e) after detecting step (d), administering a monoclonal antibody that specifically binds a Herpesvirus saimiri protein to the human patient in treatment of the diagnosed idiopathic pulmonary fibrosis.
2. The method of claim 1 , wherein the monoclonal antibody administered to the human patient is a human monoclonal antibody or a humanized monoclonal antibody.
3. A method of diagnosing and treating idiopathic pulmonary fibrosis in a human subject comprising the steps of:
(a) providing
(i) a clinical sample of a human subject who may have idiopathic pulmonary fibrosis, the clinical sample comprising lung tissue or a bronchial lavage, and
(ii) one or more monoclonal antibodies to viral proteins expressed by Herpesvirus saimiri , wherein the one or more monoclonal antibodies are specific to said Herpesvirus saimiri protein targets versus their human analogs;
(b) contacting said clinical sample (i) with said one or more monoclonal antibodies (ii);
(c) allowing binding to take place between said one or more monoclonal antibodies (ii) and said viral proteins in said clinical sample (i) if present;
(d) detecting the binding of said one or more antibodies (ii) to said viral proteins in the clinical sample (i), thereby providing a diagnosis of said human subject as having idiopathic pulmonary fibrosis; and
(e) after detecting step (d), administering a monoclonal antibody that specifically binds a Herpesvirus saimiri protein to the human patient in treatment of the diagnosed idiopathic pulmonary fibrosis.
4. The method of claim 3 , wherein one of said viral proteins is Herpesvirus saimiri IL-17.
5. The method of claim 3 , wherein one of said viral proteins is Herpesvirus saimiri DHFR.
6. The method of claim 3 , wherein one of said viral proteins is Herpesvirus saimiri cyclin D.
7. The method of claim 3 , wherein one of said viral proteins is Herpesvirus saimiri thymidylate synthase.
8. The method of claim 3 , wherein one of said viral proteins is a viral capsid protein of Herpesvirus saimiri.
9. A method of diagnosing and treating idiopathic pulmonary fibrosis comprising the steps of:
(a) providing
(i) a clinical sample from a human patient suspected of having idiopathic pulmonary fibrosis, wherein the clinical sample comprises lung tissue or bronchial lavage from the human patient, and
(ii) a labeled nucleic acid hybridization probe specific for one or more sequences of Herpesvirus saimiri;
(b) contacting said clinical sample (i) with said labeled nucleic acid probe (ii);
(c) allowing hybridization to take place between said labeled nucleic acid probe (ii) and viral sequences in said clinical sample (i) if present;
(d) detecting hybridization of said nucleic acid hybridization probe (ii) to said one or more sequences in said clinical sample (i), wherein detection of said hybridization provides a diagnosis of said human patient as having idiopathic pulmonary fibrosis; and
(e) based on the diagnosis provided in step (d), administering an antagonist of a Herpesvirus saimiri viral protein to the human patient.
10. The method of claim 9 , wherein said clinical sample comprises a paraffin embedded slide.
11. The method of claim 9 , wherein said detecting step comprises in situ hybridization or flow cytometry.
12. The method of claim 9 , wherein said providing step comprises isolation of nucleic acids from said clinical sample.
13. The method of claim 9 , further comprising a nucleic acid amplification step before said detecting step.