- Introduction
- Materials and Methods
- Ethics statement.
- Study subjects.
- Viral isolation.
- Genome sequencing.
- Nucleotide sequence accession numbers.
- Phylogenetic and selection pressure analysis.
- Viral replication kinetics.
- Isolation, stimulation of peripheral blood mononuclear cells, and DENV infections of mo-DCs.
- Flow cytometry.
- Focus-forming assays and immunostaining.
- Experimental infection of mosquitoes with DENV.
- Statistical analysis.
- Results
- Discussion
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Lineage II of Southeast Asian/American DENV-2 is Associated with a Severe Dengue Outbreak in the Peruvian Amazon
During 2010 and 2011, the Loreto region of Peru experienced a dengue outbreak of unprecedented magnitude and severity for the region. This outbreak coincided with the reappearance of dengue virus-2 (DENV-2) in Loreto after almost 8 years. Whole-genome sequence indicated that DENV-2 from the outbreak belonged to lineage II of the southeast Asian/American genotype and was most closely related to viruses circulating in Brazil during 2007 and 2008, whereas DENV-2 previously circulating in Loreto grouped with lineage I (DENV-2 strains circulating in South America since 1990). One amino acid substitution (NS5 A811V) in the 2010 and 2011 isolates resulted from positive selection. However, the 2010 and 2011 DENV-2 did not replicate to higher titers in monocyte-derived dendritic cells and did not infect or disseminate in a higher proportion of Aedes aegypti than DENV-2 isolates previously circulating in Loreto. These results suggest that factors other than enhanced viral replication played a role in the severity of this outbreak.
Author Notes
Financial support: This work was supported by the Global Emerging Infections Surveillance and Response System, a Division of the Armed Forces Health Surveillance Center (Work Unit Number 800000.82000.25GB.B0016) and the Military Infectious Diseases Research Program (Work Unit Number 6000 RAD1.S.B0302). W.L.J. and K.A.H. were supported by National Center for Research Resources Grant 5P20RR016480-12 and National Institute of General Medical Sciences Grant 8 P20 GM103451-12. N.V. was supported by start-up funds provided by the Department of Pathology, University of Texas Medical Branch and NIH contract HHSN272201000040I/HHSN27200004/D04.
Authors' addresses: Maya Williams, Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD, E-mail: maya.williams@med.navy.mil. Sandra V. Mayer and Rubing Chen, Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, E-mails: samayer@utmb.edu and ruchen@utmb.edu. William L. Johnson, Colorado School of Public Health, Fort Collins, CO, E-mail: w.johnson@rams.colostate.edu. Kathryn A. Hanley, Department of Biology, New Mexico State University, Las Cruces, NM, E-mail: khanley@nmsu.edu. Evgeniya Volkova, Laboratory of Emerging Pathogens, Food and Drug Administration Center for Biologics Evaluation and Research, Division of Emerging and Transfusion Transmitted Diseases, Bethesda, MD, E-mail: Evgeniya.volkova@fda.hhs.gov. Stalin Vilcarromero, Department of Virology, US Naval Medical Research Unit No. 6, Iquitos, Peru, E-mail: stalinf@yahoo.com. Steven G. Widen and Thomas G. Wood, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, E-mails: sgwiden@utmb.edu and tgwood@utmb.edu. Luis Suarez-Ognio, Faculty of Health Sciences, Universidad de Ciencias Aplicadas, Lima, Peru, E-mail: luis.suarez@upc.edu.pe. Kanya C. Long, Department of Biology, Andrews University, Berrien Springs, MI, E-mail: kanya@andrews.edu. Amy C. Morrison, Department of Virology, US Naval Medical Research Unit No. 6, Iquitos, Peru, and Entomology Department, University of California, Davis, CA, E-mail: amy.aegypti@gmail.com. Nikos Vasilakis, Department of Pathology, Center for Biodefense and Emerging Infectious Diseases and Institute for Human Infections and Immunity and Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX, E-mail: nivasila@utmb.edu. Eric S. Halsey, Malaria Branch, US Centers for Disease Control and Prevention, Atlanta, GA, E-mail: ehalsey@cdc.gov.