CYTOMEGALOVIRUS (CMV) APPEARS TO BE AN UBIQUITOUS VIRAL PATHOGEN.

CYTOMEGALOVIRUS (CMV) APPEARS TO BE AN UBIQUITOUS VIRAL PATHOGEN. IT IS A HIGHLY OPPORTUNISTIC AGENT AND DUE TO ITS LATENCY, AS A MEMBER OF THE HERPES FAMILY OF VIRUSES, IT CAN RECUR ABRUPTLY, ERUPTING AS A LETHAL INFECTION. THE SPECTRUM THE MORBIDITY AND MORTALITY CAUSED BY CMV INCLUDES CONGENITAL, PERINATAL, POSTNATAL, ORGAN TRANSPLANT AND TRANSFUSION INFECTIONS. CURRENT DIAGNOSIS IS NOT WELL STANDARDIZED, AND IS BASED ON THE APPEARANCE OF CYTOPATHIC EFFECT IN A SUITABLE HOST TISSUE CULTURE. TIME FOR DIAGNOSIS IS LONG (7-21 DAYS) AND SPECIFICITY IS POOR. THIS RESEARCH PROGRAM IS DESIGNED TO DEVELOP AN ENZYME EMMUNOASSAY TO RAPIDLY DETECT CMV ANTIGEN IN URINE. PHASE I FUNDING WILL ALLOW DEVELOPMENT OF MONOCLONAL ANTIBODIES TO VARIOUS POLYPEPTIDES OF THE CMV VIRIOU. IN PHASE II, THE MONOCLONAL ANTIBODIES WILL BE FULLY CHARACTERIZED AND THEN USED 1) AS TOOLS TO PURIFY CMV POLYPEPTIDES FOR USE AS IMMUNOGENS IN THE PRODUCTION OF POLYCLONAL MONOSPECIFIC ANTISERA, AND 2) AS POTENTIAL DIAGNOSTIC REAGENTS IN CONJUNCTION WITH THE POLYCLONAL REAGENTS TO DEVELOP A SENSITIVE (POLYCLONAL), SPECIFIC (MONOCLONAL), RAPID ASSAY TO DETECT CMV SHED IN THE URINE OF INFECTED INDIVIDUALS. IT IS ANTICIPATED THAT SENSITIVITY WILL HAVE TO BE GREATLY INCREASED OVER THAT OF CONVENTIONAL COLORIMETRIC ELISA'S, AND THIS WILL BE APPROACHED IN SEVERAL NOVEL WAYS BY EXAMINING OTHER ENZYMES, FLUOROGENIC SUBSTRATES, AND ALTERNATE SOLID PHASES. POTENTIAL COMMERCIAL APPLICATIONS OF SUCH AN ASSAY ARE GREAT, AS THIS NEED IS NOT CURRENTLY BEING MET. SUCH AN ASSAY COULD BE EXPECTED TO BE WIDELY USED IN PEDIATRIC WARDS, PRENATAL CLINICS, ONCOLOGY CHEMOTHERAPY SETTINGS, TRANSPLANTATION CLINICS, AND TRANSFUSION CENTERS. THIS PROPOSAL ADDRESSES THE GOALS AS OUTLINED BY THE RAPID VIRAL DIAGNOSTIC PROGRAM OF THE NIAID.