ABSTRACT
Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). 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 disease. 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.
Subject(s)
Zika Virus Infection/transmission , Zika Virus Infection/virology , Zika Virus/isolation & purification , Americas/epidemiology , Basic Reproduction Number , Brazil/epidemiology , Genetic Variation , Genome, Viral/genetics , Humans , Microcephaly/epidemiology , Microcephaly/virology , Molecular Epidemiology , Phylogeography , Spatio-Temporal Analysis , Zika Virus/genetics , Zika Virus Infection/epidemiologyABSTRACT
In previous studies from our laboratory we found that the CCl4 reactive metabolites produced during enzymatic in vitro or in vivo CCl4 biotransformation covalently bind to DNA. Further, chemically produced.CCl3 produce many adducts of unknown structure with the four DNA bases when the reaction proceeds in model systems. In the present work, we describe our attempt to elucidate by GLC/MS the structures of the adducts resulting when chemically generated.CCl3 interact with thymine. The following reaction products were identified: (i) 5-hydroxymethyl uracil; (ii) thymineglycol; (iii) 5-trichloroethyl uracil (tentative) and (iv) two isomeric 5,6-monochloro monohydroxy adducts of thymine (tentative). Reaction products found do not involve thymine positions directly participating in base-pairing processes. However, alterations in thymine structure reported if they occurred in DNA from livers of CCl4 poisoned animals, might potentially have biological significance that remains to be established.