Highly divergent dengue virus type 1 genotype sets a new distance record

Abstract

Dengue viruses (DENVs) are the leading cause of mosquito-borne viral disease of humans. They exist in both endemic and sylvatic ecotypes. In 2014, a viremic patient who had recently visited the rainforests of Brunei returned to Australia displaying symptoms consistent with DENV infection. A unique DENV strain was subsequently isolated from the patient, which we propose belongs to a new genotype within DENV serotype 1 (DENV-1). Bayesian evolutionary phylogenetic analysis suggests that the putative sylvatic DENV-1 Brunei 2014 (Brun2014) is the most divergent DENV-1 yet recorded and increases the time to the most recent common ancestor (MRCA) for DENV-1 from ≈120 years to ≈315 years. DENV-1 classification of the Brun2014 strain was further supported by monoclonal antibody serotyping data. Phenotypic characterization demonstrated that Brun2014 replication rates in mosquito cells and infection rates in Aedes aegypti mosquitoes were not significantly different from an epidemic DENV-1 strain. Given its ability to cause human illness and infect Ae. aegypti, potential urban spillover and clinical disease from further Brun2014 transmission cannot be discounted.

Archival Isolates Confirm a Single Topotype of West Nile Virus in Australia

“…This may be either a physical and environmentally favourable site, permissive of virus replication; or alternatively, a climatic or seasonal restriction resulting in a bottleneck effect. Finally, from this analysis a rate of 6.924×10 −4 nucleotide substitutions/site/year was calculated which was comparable to values calculated for West Nile virus [3], and other flaviviruses such as dengue [20], over longer genetic distances.…”

Highly Divergent Dengue Virus Type 2 in Traveler Returning from Borneo to Australia

“…Although it is tempting to estimate the time of origin of this novel DENV-2, as performed for other divergent DENV lineages ( 7 ), we have not made this estimation because our data provided strong evidence for a marked difference in evolutionary rate between human and sylvatic strains of DENV-2, which will confound all attempts at molecular clock dating. Regression analysis of root-to-tip genetic distances against time (year) of sampling suggests that sylvatic strains of DENV-2 are evolving slower than urban (human) strains, most likely because of differences in selection pressure, replication dynamics, or both, and in contrast to previous observations ( 15 ).…”

“…KX274130), as a highly divergent member of DENV-2 with a strikingly basal phylogenetic position relative to all human and sylvatic DENV-2 sequences isolated (Figure 1). This lineage is the most divergent new lineage of DENV identified, even greater than that of DENV-1 Brun2014 ( 7 ), and is located approximately midway between the genetic divergence seen at the level of serotypes and that of genotypes within serotypes.…”

“…In contrast, no sylvatic strains have been identified as DENV-3, and an early sylvatic strain of DENV-1 probably was a spillback from humans to other primates ( 6 ). However, a highly divergent sequence of DENV-1, which was isolated from a patient who had vacationed in Brunei, was recently reported ( 7 ). This virus was basal to all other strains of DENV-1 by phylogenetic analyses, which suggests the presence of another sylvatic virus lineage in Southeast Asia, albeit of unknown animal origin.…”

The mechanistic role of antibodies to dengue virus in protection and disease pathogenesis

“…A possibility is that DENV-1 and DENV-2 are genetically more diverse compared to the other DENV serotypes [14]. Another possibility is the lack of a good surrogate of protection, indicating a requirement to better define dengue immune correlates of protection, so as to identify the relevant parameters required for future vaccine potency tests.…”