The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain–Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼10⁷ plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines.

In 2010, an outbreak of febrile illness with arthralgic manifestations was detected at La Estación village, Portuguesa State, Venezuela. The etiologic agent was determined to be Mayaro virus (MAYV), a reemerging South American alphavirus. A total of 77 cases was reported and 19 were confirmed as seropositive. MAYV was isolated from acute-phase serum samples from 6 symptomatic patients. We sequenced 27 complete genomes representing the full spectrum of MAYV genetic diversity, which facilitated detection of a new genotype, designated N. Phylogenetic analysis of genomic sequences indicated that etiologic strains from Venezuela belong to genotype D. Results indicate that MAYV is highly conserved genetically, showing ≈17% nucleotide divergence across all 3 genotypes and 4% among genotype D strains in the most variable genes. Coalescent analyses suggested genotypes D and L diverged ≈150 years ago and genotype diverged N ≈250 years ago. This virus commonly infects persons residing near enzootic transmission foci because of anthropogenic incursions.

Trinidad, like many other American regions, experiences repeated epizootics of yellow fever virus (YFV). However, it is unclear whether these result from in situ evolution (enzootic maintenance) or regular reintroduction of YFV from the South American mainland. To discriminate between these hypotheses, we carried out a Bayesian phylogeographic analysis of over 100 prM/E gene sequences sampled from 8 South American countries. These included newly sequenced isolates from the recent 2008-2009 Trinidad epizootic and isolates derived from mainland countries within the last decade. The results indicate that the most recent common ancestor of the 2008-2009 epizootic existed in Trinidad 4.2 years prior to 2009 (95% highest probability density [HPD], 0.5 to 9.0 years). Our data also suggest a Trinidad origin for the progenitor of the 1995 Trinidad epizootic and support in situ evolution of YFV between the 1979 and 1988-1989 Trinidad epizootics. Using the same phylogeographic approach, we also inferred the historical spread of YFV in the Americas. The results suggest a Brazilian origin for YFV in the Americas and an overall dispersal rate of 182 km/year (95% HPD, 52 to 462 km/year), with Brazil as the major source population for surrounding countries. There is also strong statistical support for epidemiological links between four Brazilian regions and other countries. In contrast, while there were well-supported epidemiological links within Peru, the only statistically supported external link was a relatively weak link with neighboring Bolivia. Lastly, we performed a complete analysis of the genome of a newly sequenced Trinidad 2009 isolate, the first complete genome for a genotype I YFV isolate.