Please answer questions in short answer or paragraphs. Write enough to provide c
ID: 214133 • Letter: P
Question
Please answer questions in short answer or paragraphs. Write enough to provide clarity and answer each questions thoroughly in the sake of brevity. Answers should be type-written and turned in on Canvas or at the beginning of class on the specified date.
Explain how a small mutation in a virus can have large implications for transmission using Chikungunya as an example. How did the E1-226A to E1-226V mutation influence the ability of the virus to infect mosquito vectors? How did this influence transmission?
Explanation / Answer
Chikungunya virus (CHIKV) is an arbovirus which is emerging associated with the large-scale epidemics.The 2005–2006 epidemic on Reunion island that resulted in approximately 266,000 human cases was associated with a strain of CHIKV with a mutation in the envelope protein gene (E1-A226V).
To test the hypothesis that this mutation in the epidemic CHIKV (strain LR2006 OPY1) might influence fitness for different vector species, viral infectivity, dissemination, and transmission of CHIKV were compared in Aedes albopictus, the species implicated in the epidemic, and the recognized vector Ae. aegypti. Using viral infectious clones of the Reunion strain and a West African strain of CHIKV, into which either the E1–226 A or V mutation was engineered, we demonstrated that the E1-A226V mutation was directly responsible for a significant increase in CHIKV infectivity for Ae. albopictus, and led to more efficient viral dissemination into mosquito secondary organs.
The effect of the E1-A226V mutation on cholesterol dependence of CHIKV was also analyzed, revealing an association between cholesterol dependence and increased fitness of CHIKV in Ae. albopictus. Our observation that a single amino acid substitution can influence vector specificity provides a plausible explanation of how this mutant virus caused an epidemic in a region lacking the typical vector. This has important implications with respect to how viruses may establish a transmission cycle when introduced into a new area. Due to the widespread distribution of Ae. albopictus, this mutation increases the potential for CHIKV to permanently extend its range into Europe and the Americas.
To test the hypothesis that the E1-A226V mutation might influence the fitness of CHIKV in mosquito vectors, we compared the effect of this mutation on CHIKV mosquito infectivity, the ability to disseminate into heads and salivary glands, and the relative fitness in competition assays for transmission by Ae. albopictus and Ae. aegypti to suckling mice. We also analyzed the effect of the E1-A226V mutation on CHIKV cholesterol dependence for growth in mosquito C6/36 (Ae. albopictus) cells. Here we report findings that a single nucleotide change, which arose during the epidemic, significantly increases fitness of the virus for Ae. albopictus mosquitoes and was associated with CHIKV dependence on cholesterol in the mosquito cell membrane. This change likely enhanced CHIKV transmission by an atypical vector and contributed to the maintenance and scale of the epidemic.