Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum

Patton, John B.; Bennuru, Sasisekhar; Eberhard, Mark L.; Hess, Jessica A.; Torigian, April; Lustigman, Sara; Nutman, Thomas B.; Abraham, David

Urine and serum was collected from humanized mice infected for 8-12-weeks with O. volvulus for the identification of biomarkers. Infected HuSkMc mice or BLT mice were selected for this analysis so the biomarkers identified would develop in the presence of human cells thereby potentially enhancing their specificity. Several O. volvulus-specific peptides were identified in the serum and urine of BLT and HuSkMc mice (S3 Table) , however, no O. volvulusspecific proteins were found in both urine and serum from either mouse source. The most likely useful biomarkers were the proteins listed in Fig 4B. Though most of the proteins were identified by one or more unique peptide(s), among the proteins with unknown function (OVOC9087, OVOC835, OVOC224), OVOC9087 does not have orthologues in other filarial species and hence would likely be able to distinguish O. volvulus from other filarial infections. Because of the expected low number and abundance of O. volvulus-specific protein identification in the serum and urine from any given mouse in the current system, mass spectrometry was carried out with pooled serum and urine samples from each group of mice.