Adaptive Diversification Between Yellow Fever Virus West African and South American Lineages: A Genome-Wide Study

Abstract

Abstract. Yellow fever virus (YFV) has emerged as the causative agent of a vector-borne disease with devastating mortality in the tropics of Africa and the Americas. YFV phylogenies indicate that the isolates collected from West Africa, East and Central Africa, and South America cluster into different lineages and the virus spread into the Americas from Africa. To determine the nature of genetic variation accompanying the intercontinental epidemic, we performed a genome-wide evolutionary study on the West African and South American lineages of YFV. Our results reveal that adaptive genetic diversification has occurred on viral nonstructural protein 5 (NS5), which is crucially required for viral genome replication, in the early epidemic phase of these currently circulating lineages. Furthermore, major amino acid changes relevant to the adaptive diversification generally cluster in different structural regions of NS5 in a lineage-specific manner. These results suggest that YFV has experienced adaptive diversification in the epidemic spread between the continents and shed insights into the genetic determinants of such diversification, which might be beneficial for understanding the emergence and re-emergence of yellow fever as an important global public health issue.

What Does the Future Hold for Yellow Fever Virus? (II)

“…670 nt, called the “prM/E junction” [ 125 ], that encompasses 108 to 334 of the 3′ nts of the prM coding sequence, the full-length M protein coding sequence and the 337 5′ nts of the E coding sequence [ 30 , 87 , 109 , 110 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ]. However, the NS5 coding sequence and the 3′UTR are still used on some occasions [ 137 , 141 ]. As detailed in the first section of this review, there is a strong association between the phylogenetic and the geographic clustering of YFV strains so genotypes correspond to specific geographic areas that rarely overlap [ 112 ].…”

Yellow fever in Africa and the Americas: a historical and epidemiological perspective

“…YF is native to Africa where it may have emerged around 3000 years ago [ 6 ]. It probably was introduced into the Americas during the beginning of the slave trade, and benefited from favorable ecological conditions, including the presence of sylvatic vectors which, although competent, forced the virus to adapt by modifying its genome to become a pathogen close to but distinct from that of Africa [ 7 , 8 ].…”

What Does the Future Hold for Yellow Fever Virus? (I)

“…During the 'eradication' period of Aaa in South America, YFV could only circulate in sylvatic mosquito species, mostly from the Haemagogus and Sabethes genera (see subsection "In Southern America"). The extended circulation of YFV in these mosquito populations may have resulted in the selection of lineages adapted to sylvan mosquitoes which may in-turn, replicate and spread less efficiently in Aaa [127]. Although appraising vectorcompetence is challenging, the apparent susceptibility to YFV infection of Aaa mosquitoes and their ability to transmit the virus under laboratory conditions [62] suggest that a differential adaptation alone may not account for the absence of Aaa-borne outbreaks since the middle of the 20 th century in the region [85,124].…”