Viral immunogenicity determines epidemiological fitness in a cohort of DENV-1 infection in Brazil

Abstract

The dynamics of dengue virus (DENV) circulation depends on serotype, genotype and lineage replacement and turnover. In São José do Rio Preto, Brazil, we observed that the L6 lineage of DENV-1 (genotype V) remained the dominant circulating lineage even after the introduction of the L1 lineage. We investigated viral fitness and immunogenicity of the L1 and L6 lineages and which factors interfered with the dynamics of DENV epidemics. The results showed a more efficient replicative fitness of L1 over L6 in mosquitoes and in human and non-human primate cell lines. Infections by the L6 lineage were associated with reduced antigenicity, weak B and T cell stimulation and weak host immune system interactions, which were associated with higher viremia. Our data, therefore, demonstrate that reduced viral immunogenicity and consequent greater viremia determined the increased epidemiological fitness of DENV-1 L6 lineage in São José do Rio Preto.

Molecular Epidemiology of Dengue in Panama: 25 Years of Circulation

“…During the introduction of DENV-1 in 1994, Panamanian DENV-1 strains from 1995–1999 were grouped into one cluster closely related to isolates detected previously (1993) in Puerto Rico (Figure 2). Only one Panamanian isolate from 1998 clustered with Caribbean and Central American strains (Costa Rica 1993 and Puerto Rico 1996), suggesting possible co-circulation of two clusters of DENV-1 from L1, genotype V. However, several Panamanian DENV-1 strains sampled in 2004 were related to Nicaraguan and Mexican strains sampled in 2004–2006 and 2006–2008, respectively, and contained an amino acid substitution (M297T), which was previously described in L6 [16,32,33,34,35].…”

“…DENV-1 serotype has five genotypes (I to V) [15,32]. DENV-1 genotype V has been divided into three lineages (L1, L3, L6), with L1 and L6 being the most described in the Americas [16,32,33,34,35]. All sequenced Panamanian DENV-1 isolates were from genotype V, and most of them had signature amino acids of L1 [34,35], although they could be grouped into different clusters (Figure 2).…”

“…The PA B1 2015–2017 cluster was also characterized by this M297T substitution and was related to strains sampled in Central America (Nicaragua 2006–2012) and Mexico. All PA B2 2015–2017 were related to strains isolated in Colombia and Venezuela in 2004–2008 [16,32,33,34,35].…”

Emergence of genotype Cosmopolitan of dengue virus type 2 and genotype III of dengue virus type 3 in Thailand

“…If genotype replacement does occur, it will be important to see whether existing diagnostic measures work as well for the new genotype as those measures did for the previous genotype, whether the new genotype causes a larger outbreak than the previous one, and whether the disease severity changes. However, the genotype replacement of DENV may not necessarily follow automatically after the introduction of the new lineage; indeed there is precedent (in Brazil) for the failure of a newly introduced DENV-1 lineage to replace a pre-existing lineage of DENV-1 [ 71 ]. Our phylogeographic analysis also suggested repeated introduction of DENV-2 genotype Cosmopolitan into Thailand without detectable outbreaks.…”

Is Dengvaxia a useful vaccine for dengue endemic areas?

“…Recent studies have shown that viral evolution plays an important role in determining whether a person develops severe dengue disease 67. It is not yet understood how the strain of virus influences ADE, if at all, but the strain is an important risk factor influencing viraemia levels, infectivity in mosquitoes, and epidemic potential, all of which influence transmission dynamics.…”