Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak

Author(s)

Romano, Camila Malta ^{[1, 2]} ; Lauck, Michael ^[3] ; Salvador, Felipe S. ^{[1, 2]} ; Lima, Celia Rodrigues ^{[1, 2]} ; Villas-Boas, Lucy S. ^{[1, 2]} ; Araujo, Evaldo Stanislau A. ^[4] ; Levi, Jose Eduardo ^{[1, 2]} ; Pannuti, Claudio Sergio ^{[1, 2]} ; O'Connor, David ^[3] ; Kallas, Esper Georges ^[5]

Affiliation

^[1] Univ Sao Paulo, Inst Med Trop Sao Paulo, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias LIMHC, Sao Paulo - Brazil

^[3] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI - USA

^[4] Univ Sao Paulo, Fac Med, Hosp Clin, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, Disciplina Imunol Clin & Alergia LIM 60, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 8, n. 8 AUG 2 2013.
• Web of Science Citations: 24

Abstract

Background: High genetic diversity at both inter-and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. Methods and Principal Findings: We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. Conclusions and Significance: Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability. (AU)

• FAPESP's process: 10/12313-5 - Analysis of inter and intra-host genetic variability of dengue virus serotype 2 (DENV2) from patients presenting dengue fever and dengue hemorrhagic fever
• Grantee: Camila Malta Romano
• Support Opportunities: Regular Research Grants