Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil1. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 20162) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 20162). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease3. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

Identifying the genomic changes that control morphological variation and understanding how they generate diversity is a major goal of evolutionary biology. In Heliconius butterflies, a small number of genes control the development of diverse wing color patterns. Here, we used full genome sequencing of individuals across the Heliconius erato radiation and closely related species to characterize genomic variation associated with wing pattern diversity. We show that variation around color pattern genes is highly modular, with narrow genomic intervals associated with specific differences in color and pattern. This modular architecture explains the diversity of color patterns and provides a flexible mechanism for rapid morphological diversification.

Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings.

Early during the infection process, rotavirus causes the shutoff of cell protein synthesis, with the nonstructural viral protein NSP3 playing a vital role in the phenomenon. In this work, we have found that the translation initiation factor 2␣ (eIF2␣) in infected cells becomes phosphorylated early after virus infection and remains in this state throughout the virus replication cycle, leading to a further inhibition of cell protein synthesis. Under these restrictive conditions, however, the viral proteins and some cellular proteins are efficiently translated. The phosphorylation of eIF2␣ was shown to depend on the synthesis of three viral proteins, VP2, NSP2, and NSP5, since in cells in which the expression of any of these three proteins was knocked down by RNA interference, the translation factor was not phosphorylated. The modification of this factor is, however, not needed for the replication of the virus, since mutant cells that produce a nonphosphorylatable eIF2␣ sustained virus replication as efficiently as wild-type cells. In uninfected cells, the phosphorylation of eIF2␣ induces the formation of stress granules, aggregates of stalled translation complexes that prevent the translation of mRNAs. In rotavirus-infected cells, even though eIF2␣ is phosphorylated these granules are not formed, suggesting that the virus prevents the assembly of these structures to allow the translation of its mRNAs. Under these conditions, some of the cellular proteins that form part of these structures were found to change their intracellular localization, with some of them having dramatic changes, like the poly(A) binding protein, which relocates from the cytoplasm to the nucleus in infected cells, a relocation that depends on the viral protein NSP3.While every step of the translation process is amenable to regulation, under most circumstances mRNA translation primarily is regulated at the level of initiation (8). The translation of eukaryotic mRNAs involves the recognition and recruitment of mRNAs by the translation initiation machinery and the assembly of the 80S ribosome on the mRNA; this process is mediated by the eukaryotic initiation factors (eIFs). Translation initiation is a complex process that begins with the recognition of the cap nucleotide structure (m7GpppN) at the 5Ј end of mRNAs by the cap binding protein eIF4E, which is part of the cap binding complex eIF4F. This complex is composed of eIF4E, eIF4A (which is an ATP-dependent RNA helicase), and the scaffolding protein eIF4G. eIF4F functions as a capdependent RNA helicase that promotes the association of the mRNA with the 40S ribosomal subunit. The binding of MettRNA to the 40S ribosomal subunit is mediated by a ternary complex composed of eIF2-GTP-Met-tRNA (15). The release of eIFs is assisted by eIF5, which facilitates the hydrolysis of GTP carried out by eIF2. The GDP on eIF2 is exchanged for GTP by eIF2B in a regulated manner that is essential for ensuing rounds of initiation (29).Many types of stresses reduce global translation by triggering the phosphoryla...