Pathogen Detection

We have designed and optimized real-time RT-PCR assays for the detection and quantification of WNV, DENV, CHIKV and ZIKV, which are arboviruses that have caused major outbreaks in recent years. The WNV and DENV PCR assays helped define the duration of viremia in blood donors. Our collaborators Dr. Jing Jin and Dr. Graham Simmons at BSRI relied on our CHIKV PCR assay to demonstrate that neutralizing antibodies block viral infection not only at the entry step but also at the budding step. Our ZIKV PCR assay was used in a variety of studies targeted at investigating viral persistence and distribution in blood donors and animal models, as well as the characterization of viral panels for use in assay development and cross-validation.

We also developed sensitive PCR assays for Trypanosoma cruzi and Babesia microti, which are transfusion-transmitted parasites. These assays were employed in cross-sectional and longitudinal studies of blood donors to demonstrate prevalence and chronic persistence.

Selected Publications:

Hatano H, Delwart EL, Norris PJ, Lee TH, Dunn-Williams J, Hunt PW, Hoh R, Stramer SL, Linnen JM, McCune JM, Martin JN, Busch MP, Deeks SG. Evidence for persistent low-level viremia in individuals who control human immunodeficiency virus in the absence of antiretroviral therapy. J Virol 83(1):329-35 PMC2612329 (2009).

Kleinman SH, Glynn SA, Lee TH, Tobler LH, Schlumpf KS, Todd DS, Qiao H, Yu MY, Busch MP; National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study-II (NHLBI REDS-II). A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion. Blood 114(17):3677-83 PMC2766683 (2009).

Sabino EC, Lee TH, Montalvo L, Nguyen ML, Leiby DA, Carrick DM, Otani MM, Vinelli E, Wright D, Stramer SL, Busch M; NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II) International Program. Antibody levels correlate with detection of Trypanosoma cruzi DNA by sensitive polymerase chain reaction assays in seropositive blood donors and possible resolution of infection over time. Transfusion 53(6):1257-65 PMC3940448 (2013).

Lanteri MC, Lee TH, Wen L, Kaidarova Z, Bravo MD, Kiely NE, Kamel HT, Tobler LH, Norris PJ, Busch MP. West Nile virus nucleic acid persistence in whole blood months after clearance in plasma: implication for transfusion and transplantation safety. Transfusion 54(12):3232-41 PMC4268370 (2014).

Jin J, Liss NM, Chen DH, Liao M, Fox JM, Shimak RM, Fong RH, Chafets D, Bakkour S, Keating S, Fomin ME, Muench MO, Sherman MB, Doranz BJ, Diamond MS, Simmons G. Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis. Cell Rep 13(11):2553-64 PMC4720387 (2015).

Busch MP, Sabino EC, Brambilla D, Lopes ME, Capuani L, Chowdhury D, McClure C, Linnen JM, Prince H, Simmons G, Lee TH, Kleinman S, Custer B; International Component of the NHLBI Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). Transfusion-Transmitted Dengue and Associated Clinical Symptoms During the 2012 Epidemic in Brazil. J Infect Dis 213(5):694-702 PMC4747611 (2016).

Bloch EM, Levin AE, Williamson PC, Cyrus S, Shaz BH, Kessler D, Gorlin J, Bruhn R, Lee TH, Montalvo L, Kamel H, Busch MP. A prospective evaluation of chronic Babesia microti infection in seroreactive blood donors. Transfusion 56(7):1875-82 (2016).

Coffey LL, Pesavento PA, Keesler RI, Singapuri A, Watanabe J, Watanabe R, Yee J, Bliss-Moreau E, Cruzen C, Christe KL, Reader JR, von Morgenland W, Gibbons AM, Allen AM, Linnen J, Gao K, Delwart E, Simmons G, Stone M, Lanteri M, Bakkour S, Busch M, Morrison J, Van Rompay KK. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques. PLoS One 12(1):e0171148 PMC5283740 (2017).