Yellow fever virus (YFV) is the prototype member of the genus Flavivirus, a group of viruses that are transmitted between vertebrates by arthropod vectors. The virus is found in tropical regions of Africa and South America and is transmitted to primates by mosquitoes: Aedes spp. in Africa and Haemagogus and Sabethes spp. in South America. Despite the availability of an effective vaccine, yellow fever (YF) is considered a reemerging disease owing to its increased incidence in the past 25 years. Molecular epidemiologic data suggest there are seven genotypes of YFV that are geographically separated, and outbreaks of disease are more associated with particular genotypes. In addition, the risk of urban YF, owing to transmission of the virus by Aedes aegypti, is increasing in Africa, as is the potential of urban YF returning to South America. Both present serious potential public health problems to large population centers.

Yellow fever virus (YFV) remains the cause of severe morbidity and mortality in South America and Africa. To determine the evolutionary history of this important reemerging pathogen, we performed a phylogenetic analysis of the largest YFV data set compiled to date, representing the prM/E gene region from 133 viral isolates sampled from 22 countries over a period of 76 years. We estimate that the currently circulating strains of YFV arose in Africa within the last 1,500 years and emerged in the Americas following the slave trade approximately 300–400 years ago. These viruses then spread westwards across the continent and persist there to this day in the jungles of South America. We therefore illustrate how gene sequence data can be used to test hypotheses of viral dispersal and demographics, and document the role of human migration in the spread of infectious disease. Throughout the 18th and 19th centuries, yellow fever was one of the most dreaded of diseases in New and Old world port cities. Large-scale epidemics of yellow fever helped shape colonial expansion in both the Americas and in Africa, and the medical and scientific developments associated with control of the virus have been a favored topic of historians for many years. The most commonly cited hypothesis of the origin of yellow fever virus (YFV) in the Americas is that the virus was introduced from Africa, along with Aedes Aegypti mosquitoes, in the bilges of sailing vessels during the slave trade. Although the hypothesis of a slave trade introduction is often repeated, it has not been subject to rigorous examination using gene sequence data and modern phylogenetic techniques for estimating divergence times. Herein we have assembled a comprehensive data set of gene sequences for YFV, which we used to infer the time-scale and evolutionary history of YFV. These data show that the spread of YFV to the Americas corresponds closely with the routes and timing of the slave trade. Overall, this study demonstrates how molecular epidemiological studies can provide new insight into debates on the origin and spread of infectious disease.

West Nile virus (WNV) is the most widely distributed of the encephalitic flaviviruses and is a major cause of encephalitis, with isolates obtained from all continents, apart from Antarctica. Subsequent to its divergence from the other members of the Japanese encephalitis virus complex, presumably in Africa, WNV has diverged into individual lineages that mostly correspond with geographic distribution. Here we elucidate the phylogeography and evolutionary history of isolates from lineage 1 of WNV. Interestingly, there are many examples of the same amino acid having evolved independently on multiple occasions. In Africa, WNV exists in an endemic cycle, whereas it is epidemic in Europe, being reintroduced regularly from Africa either directly (in western Europe) or via the Middle East (in eastern Europe). Significantly, introduction into other geographic areas has occurred on one occasion only in each region, leading to subsequent establishment and expansion of the virus in these areas. Only one endemic genotype each is present in India and Australia, suggesting that WNV was successfully introduced into these locations once only. Each introduction occurred many centuries ago, probably due to trade and exploration during the 19th century. Likewise, in the Americas, WNV was successfully introduced in 1999 and subsequently became endemic across most temperate regions of North America (NA). In contrast to previous suggestions, an isolate from the epidemic in Israel in 1998 was not the direct progenitor of the NA epidemic; rather, both epidemics originated from the same (unknown) location.

Using a panel of neutralizing monoclonal antibodies, we have mapped epitopes in domain III of the envelope protein of the New York strain of West Nile virus. The ability of monoclonal antibodies that recognize these epitopes to neutralize virus appeared to differ between lineage I and II West Nile virus strains, and epitopes were located on the upper surface of domain III at residues E307, E330, and E332.

The surface of the mature dengue virus (DENV) particle is covered with 180 envelope (E) proteins arranged as homodimers that lie relatively flat on the virion surface. Each monomer consists of three domains (ED1, ED2, and ED3), of which ED3 contains the critical neutralization determinant(s). In this study, a large panel of DENV-2 recombinant ED3 mutant proteins was used to physically and biologically map the epitopes of five DENV complex-specific monoclonal antibodies (MAbs). All five MAbs recognized a single antigenic site that includes residues K310, I312, P332, L389, and W391. The DENV complex antigenic site was located on an upper lateral surface of ED3 that was distinct but overlapped with a previously described DENV-2 type-specific antigenic site on ED3. The DENV complex-specific MAbs required significantly higher occupancy levels of available ED3 binding sites on the virion, compared to DENV-2 type-specific MAbs, in order to neutralize virus infectivity. Additionally, there was a great deal of variability in the neutralization efficacy of the DENV complex-specific MAbs with representative strains of the four DENVs. Overall, the differences in physical binding and potency of neutralization observed between DENV complex- and type-specific MAbs in this study demonstrate the critical role of the DENV type-specific antibodies in the neutralization of virus infectivity.