Increasing Clinical Severity during a Dengue Virus Type 3 Cuban Epidemic: Deep Sequencing of Evolving Viral Populations.
Bottom Line: In conclusion, greater variability was detected during the epidemic's progression in terms of significant minority variants, particularly in the nonstructural genes.We concluded that greater variability in significant minor populations occurred as the epidemic progressed, particularly in the nonstructural genes, with higher variability observed in secondary infection cases.Remarkably, for the first time significant intrahost genetic variation was demonstrated within the same patient during the course of secondary infection with DENV-1/DENV-3, including changes in structural proteins.
Affiliation: Virology Department, Pedro Kouri Institute of Tropical Medicine, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Havana, Cuba firstname.lastname@example.org.Show MeSH
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Mentions: Synonymous and nonsynonymous variant allele rates per 10,000 bases at the complete-genome level were calculated according to time of isolation. An increasing trend toward the end of the epidemic was observed only for synonymous variant allele rates (Fig. 2). Interestingly, in terms of nonsynonymous variant alleles, the viral population analysis indicated that at position 4380 in the NS2B gene, a significant minor population (A, 0.875%; T, 0.0%; C, 0.0%; G, 99.111%) present in the first isolate collected during the epidemic (Cuba_15_2001) was selected and became predominant (A, 99.943%; T, 0.0%; C, 0.0%; G, 0.664%) at the end of the epidemic. Taking into account this pattern, variants at low frequency (<1%) were considered relevant; therefore, unique significant minority variants (>0.1%) that appeared with the epidemic's progression were analyzed using the first isolate (Cuba_15_2001) as a reference.
Affiliation: Virology Department, Pedro Kouri Institute of Tropical Medicine, PAHO/WHO Collaborating Center for the Study of Dengue and Its Vector, Havana, Cuba email@example.com.