Summary Dengue, caused by four dengue virus serotypes (DENV-1–DENV-4), is a highly-prevalent mosquito-borne viral disease in humans. Yet, selection pressures driving DENV microevolution within human hosts (‘intrahost’) remain unknown. We employed a whole-genome segmented amplification approach coupled with deep sequencing to profile DENV-3 intrahost diversity in peripheral blood mononuclear cell (PBMC) and plasma samples from 77 dengue patients. DENV-3 intrahost diversity appears to be driven by immune pressures as well as replicative success in PBMCs and potentially other replication sites. Hotspots for intrahost variation were detected in 59–78% of patients in the viral Envelope and pre-Membrane/Membrane proteins, which together form the virion surface. Dominant variants at the hotspots arose via convergent microevolution, appear to be immune-escape variants, and were evolutionarily constrained at the macro-level due to viral replication defects. Dengue is thus an example of an acute infection in which selection pressures within infected individuals drive rapid intrahost virus microevolution.

he observation of lower mean white blood cell (WBC) counts among individuals of African ancestry compared with those of European ancestry is well established. [1][2][3][4] The clinical finding of low WBC counts among healthy individuals of African ancestry is variably designated benign ethnic neutropenia and is not associated with an increased risk of infection. [5][6][7] This phenomenon is attributed, in large part, to homozygosity for the rs2814778-C variant in the promoter of ACKR1 (OMIM 613665) gene. Loss of expression of ACKR1 on cell surfaces may lead to relative neutropenia attributable to sequestration of neutrophils in peripheral tissues, including the spleen. 8 This variant is common (allele frequency, 0.96) among populations in sub-Saharan Africa but uncommon (allele frequency, 0.006) among White populations of European ancestry. [9][10][11][12][13] Approximately 63% of African American individuals, who are of mixed European and African ancestries, have the CC genotype and would be anticipated to have benign ethnic neutropenia. 9 Because reference ranges of normal values for WBC counts do not account for genotype, persons with the rs2814778-CC genotype are more likely to have a WBC count that falls below the reference range. Although many practitioners are aware of IMPORTANCE Up to two-thirds of African American individuals carry the benign rs2814778-CC genotype that lowers total white blood cell (WBC) count.OBJECTIVE To examine whether the rs2814778-CC genotype is associated with an increased likelihood of receiving a bone marrow biopsy (BMB) for an isolated low WBC count. DESIGN, SETTING, AND PARTICIPANTSThis retrospective genetic association study assessed African American patients younger than 90 years who underwent a BMB at

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Abstract. Chikungunya is caused by the mosquito-borne arthrogenic alphavirus, chikungunya virus (CHIKV). Chikungunya was introduced into the Americas in late 2013 and Nicaragua in mid-2014. Here, we sequenced five imported and 30 autochthonous Nicaraguan CHIKV from cases identified in the first epidemic in the country between August 2014 and April 2015. One full-length and two partial genomic sequences were obtained by deep sequencing; Sanger methodology yielded 33 E1 sequences from five imported and 28 autochthonous cases. Phylogenetic analysis indicates that Nicaraguan CHIKV all belonged to the Asian genotype, Caribbean clade. Moreover, E1 gene sequences revealed accumulation of mutations in later months of the epidemic, including four silent mutations in 11 autochthonous cases and three non-synonymous mutations in three autochthonous cases. No mutations contributing to increased transmissibility by Aedes albopictus were identified in the E1 gene. This represents the most comprehensive set of CHIKV sequences available from the Americas to date.