부산대학교 도서관

Variability in how individuals respond to pathogens is a hallmark of infectious disease, yet the basis for individual variation in host response is often poorly understood. The titer of infectious virus among individual mosquitoes infected with arboviruses is frequently observed to vary by several orders of magnitude in a single experiment, even when the mosquitoes are highly inbred. To better understand the basis for this titer variation, we sequenced populations of Sindbis virus (SINV) obtained from individual infected Aedes aegypti mosquitoes that, despite being from a highly inbred laboratory colony, differed in their titers of infectious virus by approximately 10,000-fold. We observed genetic differences between these virus populations that indicated the virus present in the midguts of low titer mosquitoes was less fit than that of high titer mosquitoes, possibly due to founder effects that occurred during midgut infection. Furthermore, we found dramatic differences in the specific infectivity or SI (the ratio of infectious units/viral genome equivalents) between these virus populations, with the SI of low titer mosquitoes being up to 10,000-fold lower than that of high titer mosquitoes. Despite having similar amounts of viral genomes, low titer mosquitoes appeared to contain less viral particles, suggesting that viral genomes were packaged into virions less efficiently than in high titer mosquitoes. Finally, antibiotic treatment, which has been shown to suppress mosquito antiviral immunity, caused an increase in SI. Our results indicate that the extreme variation that is observed in SINV infectious titer between individual Ae. aegypti mosquitoes is due to both genetic differences between virus populations and to differences in the proportion of genomes that are packaged into infectious particles. Author summary: Individual hosts typically respond differently to virus infection. These differences are usually attributed to genetic variation between hosts or differences between virus strains. However, when highly inbred mosquitoes are infected with an arbovirus, individual mosquitoes still often vary widely in titer of infectious virus. We examined the virus populations in individual Aedes aegypti mosquitoes infected with Sindbis virus that differed by approximately 10,000-fold in the amount of infectious virus. Based on our experiments, we have made two important findings. First, we found genetic differences between these virus populations, suggesting that viruses in low titer mosquitoes were less fit than those in high titer mosquitoes, potentially due to genetic founder effects. Second, we also found that the amounts of viral genomes did not vary significantly between low and high titer mosquitoes, despite huge differences in the amount of infectious virus. Furthermore, the proportion of viral genomes packaged into infectious particles was improved by feeding the mosquitoes antibiotics, which has been shown to suppress antiviral immunity. These findings have important implications regarding our understanding of the transmission of arboviral disease. [ABSTRACT FROM AUTHOR]