Browsing by Author "Carrington, Christine V. F."

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    Determinants of dengue virus dispersal in the Americas
    Allicock, Orchid M.; Sahadeo, Nikita; Lemey, Philippe; Auguste, A. Jonathan; Suchard, Marc A.; Rambaut, Andrew; Carrington, Christine V. F. (Oxford University Press, 2020-07)
    Dengue viruses (DENVs) are classified into four serotypes, each of which contains multiple genotypes. DENV genotypes introduced into the Americas over the past five decades have exhibited different rates and patterns of spatial dispersal. In order to understand factors underlying these patterns, we utilized a statistical framework that allows for the integration of ecological, socioeconomic, and air transport mobility data as predictors of viral diffusion while inferring the phylogeographic history. Predictors describing spatial diffusion based on several covariates were compared using a generalized linear model approach, where the support for each scenario and its contribution is estimated simultaneously from the data set. Although different predictors were identified for different serotypes, our analysis suggests that overall diffusion of DENV-1, -2, and -3 in the Americas was associated with airline traffic. The other significant predictors included human population size, the geographical distance between countries and between urban centers and the density of people living in urban environments.
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    Effects of Chikungunya virus immunity on Mayaro virus disease and epidemic potential
    Webb, Emily M.; Azar, Sasha R.; Haller, Sherry L.; Langsjoen, Rose M.; Cuthbert, Candace E.; Ramjag, Anushka T.; Luo, Huanle; Plante, Kenneth; Wang, Tian; Simmons, Graham; Carrington, Christine V. F.; Weaver, Scott C.; Ross, Shannan L.; Auguste, A. Jonathan (Springer Nature, 2019)
    Mayaro virus (MAYV) causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), an evolutionary relative in the Semliki Forest virus complex of alphaviruses. MAYV emergence is typically sporadic, but recent isolations and outbreaks indicate that the virus remains a public health concern. Given the close phylogenetic and antigenic relationship between CHIKV and MAYV, and widespread distribution of CHIKV, we hypothesized that prior CHIKV immunity may affect MAYV pathogenesis and/or influence its emergence potential. We pre-exposed immunocompetent C57BL/6 and immunocompromised A129 or IFNAR mice to wild-type CHIKV, two CHIKV vaccines, or a live-attenuated MAYV vaccine, and challenged with MAYV. We observed strong cross-protection against MAYV for mice pre-exposed to wild-type CHIKV, and moderately but significantly reduced cross-protection from CHIKV-vaccinated animals. Immunity to other alphavirus or flavivirus controls provided no protection against MAYV disease or viremia. Mechanistic studies suggested that neutralizing antibodies alone can mediate this protection, with T-cells having no significant effect on diminishing disease. Finally, human sera obtained from naturally acquired CHIKV infection cross-neutralized MAYV at high titers in vitro. Altogether, our data suggest that CHIKV infection can confer cross-protective effects against MAYV, and the resultant reduction in viremia may limit the emergence potential of MAYV.
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    Isolation of a novel insect-specific flavivirus with immunomodulatory effects in vertebrate systems
    Auguste, A. Jonathan; Langsjoen, Rose M.; Porier, Danielle L.; Erasmus, Jesse H.; Bergren, Nicholas A.; Bolling, Bethany G.; Luo, Huanle; Singh, Ankita; Guzman, Hilda; Popov, Vsevolod L.; da Rosa, Amelia P. A. Travassos; Wang, Tian; Kang, Lin; Allen, Irving C.; Carrington, Christine V. F.; Tesh, Robert B.; Weaver, Scott C. (2021-10)
    We describe the isolation and characterization of a novel insect-specific flavivirus (ISFV), tentatively named Aripo virus (ARPV), that was isolated from Psorophora albipes mosquitoes collected in Trinidad. The ARPV genome was determined and phylogenetic analyses showed that it is a dual host associated ISFV, and clusters with the main mosquito-borne flaviviruses. ARPV antigen was significantly cross-reactive with Japanese encephalitis virus serogroup antisera, with significant cross-reactivity to Ilheus and West Nile virus (WNV). Results suggest that ARPV replication is limited to mosquitoes, as it did not replicate in the sandfly, culicoides or vertebrate cell lines tested. We also demonstrated that ARPV is endocytosed into vertebrate cells and is highly immunomodulatory, producing a robust innate immune response despite its inability to replicate in vertebrate systems. We show that prior infection or coinfection with ARPV limits WNV-induced disease in mouse models, likely the result of a robust ARPV-induced type I interferon response.
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    Phylogenetic characterization of Orthobunyaviruses isolated from Trinidad shows evidence of natural reassortment
    Foster, Jerome E.; Lopez, Krisangel; Eastwood, Gillian; Guzman, Hilda; Carrington, Christine V. F.; Tesh, Robert B.; Auguste, A. Jonathan (Springer, 2023-02)
    The genus Orthobunyavirus is a diverse group of viruses in the family Peribunyaviridae, recently classified into 20 serogroups, and 103 virus species. Although most viruses within these serogroups are phylogenetically distinct, the absence of complete genome sequences has left several viruses incompletely characterized. Here we report the complete genome sequences for 11 orthobunyaviruses isolated from Trinidad, French Guiana, Guatemala, and Panama that were serologically classified into six serogroups and 10 species. Phylogenetic analyses of these 11 newly derived sequences indicate that viruses belonging to the Patois, Capim, Guama, and Group C serocomplexes all have a close genetic origin. We show that three of the 11 orthobunyaviruses characterized (belonging to the Group C and Bunyamwera serogroups) have evidence of histories of natural reassortment through the M genome segment. Our data also suggests that two distinct lineages of Group C viruses concurrently circulate in Trinidad and are transmitted by the same mosquito vectors. This study also highlights the importance of complementing serological identification with nucleotide sequencing when characterizing orthobunyaviruses.