Surrogate markers for viral infections and other inflammatory responses

Abstract

Compositions and methods for the detection, diagnosis and treatment of BVDV and other viruses are provided.

1 . A method for diagnosing BVDV in a ruminant test animal comprising: 
 a) obtaining a biological sample from a test animal and from a non-BVDV infected animal;    b) contacting said sample with an agent having affinity for at least one differentially expressed BVDV surrogate marker shown in Tables 1-9; and    d) diagnosing the presence of BVDV via detection of at least one differentially expressed BVDV surrogate marker, an alteration in the expression level of said BVDV surrogate marker obtained from said test animal, relative to that obtained from said non-BVDV infected animal being indicative of BVDV in said test animal.    
   
   
       2 . The method of  claim 1 , wherein said at least one BVDV surrogate marker is a nucleic acid and said expression level is up-regulated in response to BVDV infection.  
   
   
       3 . The method of  claim 1 , wherein said at least one BVDV surrogate marker is a nucleic acid and said expression level is down-regulated in response to BVDV infection.  
   
   
       4 . The method of  claim 1 , wherein said at least one BVDV surrogate marker is a nucleic acid immobilized on a gene chip.  
   
   
       5 . The method of  claim 1 , wherein said biological sample is selected from the group consisting of blood, urine, skin, serum, milk, sputumr, saliva, and tears.  
   
   
       6 . The method of  claim 1  wherein said biological sample comprises blood cells or skin cells which are lysed to release nucleic acids therein.  
   
   
       7 . The method of  claim 6 , wherein said released nucleic acids are amplified.  
   
   
       8 . The method of  claim 1 , wherein said ruminant animal is a persistently infected steer or heifer and at least one BVDV surrogate marker is a nucleic acid which is upregulated and is selected from the group consisting of CK945739, CK777968,NM — 173941 and CK 960499. which is upregulated and is selected from the group consisting of CK 945739, CK777968, NM — 173941 and CK960499.  
   
   
       9 . The method of  claim 1 , wherein said ruminant animal is a persistently infected steer and at least one BVDV surrogate marker is a nucleic acid which is downregulated and is selected from the group consisting of CK848330, BP 102272, AU278490 and BE723387.  
   
   
       10 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a persistently infected fetus and at least one BVDV surrogate marker is a nucleic acid which is upregulated and is selected from the group consisting of CK977019, CA923353, CB461169, and CB445920.  
   
   
       11 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a persistently infected fetus and at least one BVDV surrogate marker is a nucleic acid which is down regulated and is selected from the group consisting of NM — 175827, CB425639, NM — 174511 and CB534503.  
   
   
       12 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a transiently infected fetus and at least one BVDV surrogate marker is a nucleic acid which is upregulated and is selected from the group consisting of CK960499, CB464371, NM — 174366, and CB433489.  
   
   
       13 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a transiently infected fetus and at least one BVDV surrogate marker is a nucleic acid which is down regulated and is selected from the group consisting of CB444277, AB008573, CB433789 and AV609250.  
   
   
       14 . A gene chip for performing the method of  claim 1  comprising a plurality of BVDV surrogate markers selected from the group consisting of CK945739, CK777968, NM — 173941, CK960499, CK848330, BP102272, AU278490, BE1723387, CK977019, CA923353, CB461169, CB445920, NM — 175827, CB425639, NM — 174511, CB534503. CK960499, CB464371, NM — 174366, CB433489, CB444277, AB008573, CB433789 and AV609250.  
   
   
       15 . The method of  claim 1 , wherein said at least one BVDV surrogate marker is a polypeptide and said expression level is up-regulated in response to BVDV infection.  
   
   
       16 . The method of  claim 1 , wherein said at least one BVDV surrogate marker is a polypeptide and said expression level is down-regulated in response to BVDV infection.  
   
   
       17 . The method of  claim 1 , wherein said at least one BVDV surrogate marker is a polypeptide or fragment thereof immobilized on a solid support.  
   
   
       18 . The method of  claim 1 , wherein said ruminant animal is a persistently infected steer and at least one BVDV surrogate marker is a polypeptide or fragments thereof which is upregulated and is selected from the group consisting of polypeptides thereof encoded by CK945739, CK777968, NM — 173941 and CK960499.  
   
   
       19 . The method of  claim 1 , wherein said ruminant animal is a persistently infected steer and at least one BVDV surrogate marker is a polypeptide or fragments thereof which is downregulated and is selected from the group consisting of polypeptides encoded by CK848330, BP102272, AU278490 and BE723387.  
   
   
       20 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a persistently infected fetus and at least one BVDV surrogate marker is a polypeptide or fragment thereof which is upregulated and is selected from the group consisting of polypeptides encoded by CK977019, CA923353, CB461169, and CB445920.  
   
   
       21 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a persistently infected fetus and at least one BVDV surrogate marker is a polypeptide or fragment thereof which is down regulated and is selected from the group consisting of polypeptides encoded by NM — 175827, CB425639, NM — 174511 and CB534503.  
   
   
       22 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a transiently infected fetus and at least one BVDV surrogate marker is a polypeptide or fragment thereof which is upregulated and is selected from the group consisting of polypeptides encoded by CK960499, CB464371, NM — 174366, and CB433489.  
   
   
       23 . The method of  claim 1 , wherein said ruminant animal is a heifer carrying a transiently infected fetus and at least one BVDV surrogate marker is a polypeptide or fragment thereof which is down regulated and is selected from the group consisting of polypeptides encoded by CB444277, AB008573, CB433789 and AV609250.  
   
   
       24 . A solid support for performing the method of  claim 1  comprising a plurality of BVDV surrogate polypeptide markers selected from the group consisting of polypeptides encoded by CK945739, CK777968, NM — 173941, CK960499, CK848330, BP102272, AU278490, BE723387, CK977019, CA923353, CB461169, CB445920, NM — 175827, CB425639, NM — 174511, CB534503. CK960499, CB464371, NM — 174366, CB433489, CB444277, AB008573, CB433789 and AV609250.  
   
   
       25 . The method of  claim 1 , wherein said ruminant test animal is selected from the group consisting of a bovine a steer, a pregnant bovine, a bovine fetus and a bovine calf.  
   
   
       26 . The method of  claim 1 , wherein said agent having affinity for said BVDV surrogate marker is selected from the group consisting of at least one nucleic acid which specifically hybridizes with at least one nucleic acid shown in Tables 1-9, and an antibody immunologically specific for at least one polypeptide encoded by a nucleic acid shown in Tables 1-9.  
   
   
       27 . The method of  claim 26 , wherein said agent is detectably labeled.  
   
   
       28 . A kit for differentially diagnosing BVDV infection via the method of  claim 1 , comprising at least one BVDV surrogate marker detector molecule, and reagents for detection of the same said optionally comprising a gene chip comprising a plurality of BVDV surrogate markers selected from the group consisting of CK945739, CK777968, NM_173941, CK960499, CK848330, BP102272, AU278490, BE723387, CK977019, CA923353, CB461169, CR445920, NM — 175827, CB425639, NM — 174511, CB534503. CK960499, CB464371, NM — 174366, CB433489, CB444277, AB008573, CB433789 and AV609250 or a solid support comprising a plurality of BVDV surrogate polypeptide markers selected from the group consisting of polypeptides encoded by CK945739, CK777968, NM — 173941, CK960499, CK848330, BP102272, AU278490, BE723387, CK977019, CA923353, CB461169, CB445920, NM — 175827, CB425639, NM — 174511, CB534503. CK960499, CB464371, NM — 174366, CB433489, CB444277, AB008573, CB433789 and AV609250.  
   
   
       29 . The kit of  claim 28 , wherein said BVDV surrogate marker detector molecule is selected from the group consisting of a probe or primer which specifically hybridizes with a BVDV surrogate marker nucleic acid, and an antibody which specifically binds to a BVDV surrogate marker polypeptide.  
   
   
       30 . A method as claimed in  claim 1  further comprising detection of markers associated with transient or acute BVDV infection.  
   
   
       31 . A method for identifying agents useful for the treatment of viral infections, comprising: 
 a) providing a host cell expressing at least BVDV surrogate marker in Tables 1-9 which is differentially expressed in response to viral infection and exposing said cell to an RNA virus under conditions suitable for infection to occur;    b) incubating said host cells in the presence and absence of said agent; and    c) identifying those agents which modulate the expression of at least one BVDV surrogate marker in treated cells when compared to untreated cells.    
   
   
       32 . A method for detecting viral surrogate marker molecules in a test animal comprising: 
 a) obtaining a plurality of biological samples from said test animal and from a non-virally infected animal;    b) contacting said biological sample with a composition comprising one or more viral surrogate marker molecule detection reagents in an amount effective to permit detection and quantitation of a viral surrogate molecule, if present, in said sample; and    c) determining from b) the amount of said viral surrogate marker molecule, wherein an alteration of levels of said viral surrogate marker molecule, relative to those obtained from non-virally infected animals, is indicative of viral infection in said test animal.    
   
   
       33 . The method of  claim 32 , wherein a lack of alteration of levels of said viral surrogate marker molecule indicates that the test animal is not virally infected.  
   
   
       34 . The method of  claim 32 , wherein said viral surrogate marker molecule is increased in a test subject infected with a virus selected from the group consisting of BVDV, Influenza, HIV, Ebola virus, FcLv, FIP virus, Bluetongue virus, West Nile Virus, hepatitis C Virus and Epizootic Hemorrhagic Disease Virus.