| Description |
Yellow fever virus (YFV) is a reemerging disease affecting 200,000 people annually in Africa and South America. In order to investigate genetic factors underlying YFV susceptibility, I studied Toll-like receptor (TLR) 7 and TLR8 in primates that live within the same geographic region and share the pathogenic pressure of YFV. In all primates, single-stranded RNA (ssRNA) viruses such as YFV are detected by TLR7 and TLR8, making them likely candidates for mediation of YFV susceptibility. In 2007-2009, a major YFV outbreak in Northern Argentina decimated howler monkey (Alouatta) populations. I explored the relationship between TLR7 and TLR8 genes and YFV susceptibility using samples from Alouatta individuals alive before the YFV outbreak, individuals that were exposed to the outbreak, individuals alive after the outbreak, as well as nearby human populations. I compared patterns of selection on the genus Alouatta to other primates, measured genetic divergence between Alouatta YFV exposure groups, and evaluated genetic differences in Alouatta for functional consequences. I also used published DNA sequences from Native Americans to measure positive selection and differentiation of sites within TLR7 and TLR8 in populations in YFV endemic areas. While I did not identify common sites under selection in humans and howler monkeys, I discovered 1) that TLR7 is under strong purifying selection in the Alouatta genus; 2) that the species Alouatta guariba clamitans has positively selected sites within functionally important TLR7 regions not seen in any other primates; 3) that in Native American human populations in YFV endemic areas, the minor allele at rs179008 in TLR7, associated with progression of ssRNA viruses, is at the greatest frequency. |
