Triaging patients with acute febrile illness, particularly with haemorrhagic fever, can provide better clinical focus and assessment of medical countermeasures. Identifying unique molecular signatures associated with a particular infection and each stage of subsequent disease – such as acute phase through to decline or recovery, would be of predictive value. For most infectious diseases a blood sample is easiest to obtain and usually the most informative. In most cases translating data to an easily applicable ELISA is most clinically relevant. Therefore, proteomics provides an ideal avenue to characterise real world samples. In order to evaluate whether this type of approach – from samples to predictive capability, patients with hantavirus were characterised using a proteomic approach.
Haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas (HPS) are caused by hantaviruses. Clinical symptoms of HRFS can range from headaches and fever to thrombocytopenia and acute kidney injury. Two hantaviruses, Dobrava (DOBV) and Puumala (PUUV) cause HFRS disease in humans. PUUV infection usually has a mild clinical path with a case fatality rate < 1%. DOBV has a case fatality rate of approximately 10%. The pathogenesis behind the variance in severity of infection between individuals infected with different hantavirus genotypes is poorly understood.
Longitudinal plasma samples from 12 individuals with either mild or severe DOBV or PUUM were compared with healthy controls (n=5) using a high-resolution label free proteomics approach. Changes in the plasma proteome pointed to underlying biological consequences. From these, several proteins, including SPINK1, APOF, HPR and CFHR1 were identified as potential prognostic biomarkers for severe disease. Comparing the hantavirus profiles found here to the plasma proteomes of individuals exposed to other pathogens (e.g. EBOV and spirochetes) will stratify biomarkers for hantavirus that in turn will enhance the diagnosis and prognosis of this emerging pathogen.