Association of Dengue Virus Serotypes 1&2 with Severe Dengue Having Deletions in Their 3′Untranslated Regions (3′UTRs)

Abstract

Dengue virus infections are recorded as hyper-endemic in many countries, including India. Research pertaining to the reasons for frequent outbreaks and severe dengue is ongoing. Hyderabad city, India, has been recorded as a ‘hotspot’ for dengue virus infections. Dengue virus strains circulating over the past few years in Hyderabad city have been characterized at the molecular level to analyze the serotype/genotypes; 3′UTRs were further amplified and sequenced. The disease severity in patients infected with dengue virus strains with complete and 3′UTR deletion mutants was analyzed. Genotype I of the serotype 1 replaced genotype III, which has been circulating over the past few years in this region. Coincidentally, the number of dengue virus infections significantly increased in this region during the study period. Nucleotide sequence analysis suggested twenty-two and eight nucleotide deletions in the 3′UTR of DENV-1. The eight nucleotide deletions observed in the case of DENV-1 3′UTR were the first reported in this instance. A 50 nucleotide deletion was identified in the case of the serotype DENV-2. Importantly, these deletion mutants were found to cause severe dengue, even though they were found to be replication incompetent. This study emphasized the role of dengue virus 3′UTRs on severe dengue and emerging outbreaks.