TY - JOUR
T1 - Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti
AU - Reitmayer, Christine M.
AU - Levitt, Emily
AU - Basu, Sanjay
AU - Atkinson, Barry
AU - Fragkoudis, Rennos
AU - Merits, Andres
AU - Lumley, Sarah
AU - Larner, Will
AU - Diaz, Adriana V.
AU - Rooney, Sara
AU - Thomas, Callum J.E.
AU - von Wyschetzki, Katharina
AU - Rausalu, Kai
AU - Alphey, Luke
N1 - Publisher Copyright:
Copyright © 2023 the Author(s).
PY - 2023
Y1 - 2023
N2 - Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1–nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.
AB - Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1–nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.
KW - alphaviruses
KW - arbovirus transmission
KW - nsP2 protease
KW - superinfection exclusion
UR - http://www.scopus.com/inward/record.url?scp=85169767092&partnerID=8YFLogxK
U2 - 10.1073/pnas.2303080120
DO - 10.1073/pnas.2303080120
M3 - Article
C2 - 37669371
AN - SCOPUS:85169767092
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 37
M1 - e2303080120
ER -