Reversal of viral-induced systemic shock and respiratory distress by blockade of the lymphotoxin beta pathway

1. A method of inducing an antiviral response or treating a viral infection in an individual suffering from viral-induced systemic shock mediated by CD8 T cells and/or viral-induced pulmonary distress mediated by CD8 T cells, comprising administering to the individual an effective amount of a pharmaceutical composition comprising a lymphotoxin-beta (LT-beta) or lymphotoxin-beta receptor (LT-beta-R) blocking agent selected from the group consisting of an antibody directed against LT-beta, a soluble LT-beta-R, an antibody directed against LT-beta-R, and an antibody directed against surface LT ligand, and a pharmaceutically acceptable carrier, such that an antiviral response is induced or viral infection treatment occurs.

2. The method of claim 1 , wherein the composition comprises a soluble LT-beta-R or an anti-LT-beta-R antibody which binds LT-beta-R.

3. A method of treating viral-induced systemic shock mediated by CD8 T cells in an individual comprising administering to the individual an effective amount of a pharmaceutical composition comprising a lymphotoxin-beta (LT-beta) or lymphotoxin-beta receptor (LT-beta-R) blocking agent selected from the group consisting of a an antibody directed against LT-beta, a soluble LT-beta-R, an antibody directed against LT-beta-R, and an antibody directed against surface LT ligand, and a pharmaceutically acceptable carrier, such that viral-induced systemic shock is treated.

4. The method of claim 3 , wherein the composition comprises a soluble LT-beta-R or an anti-LT-beta-R antibody which binds LT-beta-R.

5. A method of treating viral-induced pulmonary distress mediated by CD8 T cells in an individual comprising administering to the individual an effective amount of a pharmaceutical composition comprising a lymphotoxin-beta (LT-beta) or lymphotoxin-beta receptor (LT-beta-R) blocking agent selected from the group consisting of an antibody directed against LT-beta, a soluble LT-beta-R, an antibody directed against LT-beta-R, and an antibody directed against surface LT ligand, and a pharmaceutically acceptable carrier, such that viral-induced pulmonary distress is treated.

6. The method of claim 5 , wherein the composition comprises a soluble LT-beta-R or an anti-LT-beta-R antibody which binds LT-beta-R.

7. The method of any of claims 2 , 4 or 6 , wherein the soluble LT-beta-R comprises a LT-beta-R/immunoglobulin fusion (Ig fusion) protein.

8. The method of any of claims 1 , 3 or 5 wherein the soluble LT-beta-R comprises a ligand binding domain that can selectively bind to surface LT ligand.

9. The method of any of claims 1 , 2 , 3 , 4 , 5 or 6 , wherein said individual is infected with Sin Nombre Virus, Marburg virus, Lassa virus, or Dengue virus.

10. The method of any of claims 1 , 3 or 5 , wherein the soluble LT-beta-R comprises a soluble human LT-beta-R.

11. The method of claim 10 , wherein the soluble human LT-beta-R is fused to one or more heterologous protein domains.

12. The method of claim 11 , wherein the heterologous protein domain is selected from the group consisting of immunoglobulins, serum albumin, lipoproteins, apolipoproteins and transferrin.

13. The method of claim 11 , wherein the heterologous protein domain comprises a human immunglobulin Fc domain.

14. The method of claim 8 , wherein the ligand binding domain comprises a functional fragment of soluble human LT-beta-R sequence encoding an LT-beta-R ligand binding domain.

15. A method of inducing an antiviral response in a human suffering from viral-induced systemic shock mediated by CD8 T cells and/or viral-induced pulmonary distress mediated by CD8 T cells, comprising administering to the human a pharmaceutical composition comprising a polypeptide that comprises a soluble ligand binding domain of human LT-beta-R fused to a human IgG Fc domain and a pharmaceutically acceptable carrier, such that an antiviral response is induced.

16. The method of claim 15 , wherein the ligand binding domain comprises the sequence of the extracellular portion of human LT-beta-R.

17. The method of any of claim 15 , wherein the ligand binding domain comprises an extracellular region of the human LT-beta-R sequence.

18. The method of any of claim 15 , wherein the ligand binding domain consists essentially of the soluble human LT-beta-R sequence.

19. A method of inducing an antiviral response or treating viral infection in an individual infected with Sin Nombre Virus (SNV) who is suffering from viral-induced pulmonary distress, comprising administering to the individual an effective amount of a pharmaceutical composition comprising an LT-beta blocking agent comprising either an antibody directed against LT-beta or an antibody directed against surface LT ligand, and a pharmaceutically acceptable carrier, such that an antiviral response is induced or viral infection treatment occurs.

20. A method of inducing an antiviral response or treating viral infection in an individual infected with Sin Nombre Virus (SNV) who is suffering from viral-induced pulmonary distress, comprising administering to the individual an effective amount of a pharmaceutical composition comprising a soluble LT-beta-R, and a pharmaceutically acceptable carrier, such that an antiviral response is induced or viral infection treatment occurs.

21. A method of treating a viral infection in an individual infected with Sin Nombre Virus (SNV) who is suffering from viral-induced systemic shock, comprising administering to the individual an effective amount of a pharmaceutical composition comprising a soluble LT-beta-R, and a pharmaceutically acceptable carrier, such that viral infection treatment occurs.

22. The method of claim 20 or 21 , wherein the soluble LT-beta-R is fused to one or more heterologous protein domains.

23. The method of claim 20 , wherein the heterologous protein domain is a human immunglobulin Fc domain.

24. The method of claim 20 or 21 , wherein the ligand binding domain comprises a functional fragment of soluble human LT-beta-R sequence encoding an LT-beta-R ligand binding domain.

25. The method of claim 20 or 21 , wherein the soluble lymphotoxin-beta-R comprises a ligand binding domain that can selectively bind to surface LT ligand.

26. The method of claim 22 , wherein the heterologous protein domain is selected from the group consisting of immunoglobulins, serum albumin, lipoproteins, apolipoproteins and transferrin.

27. The method of claim 8 , wherein the ligand binding domain comprises the sequence of the extracellular portion of human LT-beta-R.

28. The method of claim 8 , wherein the ligand binding domain comprises an extracellular region of the human LT-beta-R sequence.