Novel routes for cytomegalovirus diagnosis and treatment
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Human cytomegalovirus (HCMV) represents a massive burden on infected individuals and healthcare systems worldwide. Though HCMV is not normally disease causing in healthy individuals, it poses a significant threat to immunocompromised people and developing fetuses, causing a broad range of diseases due to its ability to infect several organ and tissue types. Current diagnostic and treatment modalities for HCMV are extremely limited in their scope. In the United States, HCMV testing is typically only done when one presents with possible HCMV-caused symptoms, as current methods are deemed unwarranted if no symptoms are presented in a patient. Additionally, if treatment is to be given, current antiviral drugs are limited to targeting only one aspect of HCMV’s replication cycle and, at times, can be rather toxic. As such, continued research and development is needed to create rapid, facile point–of-care diagnostics as well as identify new druggable targets to lessen the impact of infection. Utilizing a murine model system to study HCMV infection, we recently showed that precise detection of murine cytomegalovirus (MCMV) from the urine of infected mice was rapidly achieved through the use of a novel electrochemical immunoassay. By attaching glucose oxidase to an antibody recognizing MCMV, we readily detected MCMV at an electrode using chemistry similar to that used in modern day glucometers. Additionally, we characterized and identified a major role for a uniquely structured MCMV deubiquitinating enzyme (DUB) during infection. When the virus lacked DUB activity, levels of a virally encoded pro-inflammatory chemokine increased, leading to the mutant DUB virus’ dramatic attenuation in mice. As this enzyme is incredibly important for MCMV pathogenesis and is highly conserved between MCMV and HCMV, it may serve as a viable target for antiviral therapies. Because HCMV infections persist for the lifetime of the individual, continued success in diagnosis and treatment of HCMV will be needed as long as humans exist as a species.