Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

Author:

Bennuru Sasisekhar1,Cotton James A.2,Ribeiro Jose M. C.3,Grote Alexandra4,Harsha Bhavana2,Holroyd Nancy2,Mhashilkar Amruta5,Molina Douglas M.6,Randall Arlo Z.6,Shandling Adam D.6,Unnasch Thomas R.5,Ghedin Elodie47,Berriman Matthew2,Lustigman Sara8,Nutman Thomas B.1

Affiliation:

1. Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA

2. Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom

3. Laboratory of Malaria and Vector Research, NIAID, NIH, Rockville, Maryland, USA

4. Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York, USA

5. University of South Florida, Tampa, Florida, USA

6. Antigen Discovery Inc., Irvine, California, USA

7. College of Global Public Health, New York University, New York, New York, USA

8. New York Blood Center, New York, New York, USA

Abstract

ABSTRACT Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont ( w Ov). In so doing, we have identified stage-specific pathways important to the parasite’s adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs. IMPORTANCE The global onchocerciasis (river blindness) elimination program will have to rely on the development of new tools (drugs, vaccines, biomarkers) to achieve its goals by 2025. As an adjunct to the completed genomic sequencing of O. volvulus , we used a comprehensive proteomic and transcriptomic profiling strategy to gain a comprehensive understanding of both the vector-derived and human host-derived parasite stages. In so doing, we have identified proteins and pathways that enable novel drug targeting studies and the discovery of novel vaccine candidates, as well as useful biomarkers of active infection.

Funder

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Bill and Melinda Gates Foundation

in part by HHS | NIH | National Institute of Allergy and Infectious Diseases

the Wellcome Trust through core funding of the Wellcome Trust Sanger Institute

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference65 articles.

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2. WHO. 2016. Investing to overcome the global impact of neglected tropical diseases: third WHO report on negelected tropical diseases. World Health Organization, Geneva, Switzerland.

3. Centers for Disease Control and Prevention (CDC). 2013. Progress toward elimination of onchocerciasis in the Americas—1993–2012. MMWR Morb Mortal Wkly Rep 62:405–408. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6220a4.htm.

4. African programme for onchocerciasis control: progress report, 2013–2014;WHO;Wkly Epidemiol Rec,2014

5. Elimination and Eradication of Neglected Tropical Diseases with Mass Drug Administrations: A Survey of Experts

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