Cooler Temperatures Destabilize RNA Interference and Increase Susceptibility of Disease Vector Mosquitoes to Viral Infection

Abstract

BackgroundThe impact of global climate change on the transmission dynamics of infectious diseases is the subject of extensive debate. The transmission of mosquito-borne viral diseases is particularly complex, with climatic variables directly affecting many parameters associated with the prevalence of disease vectors. While evidence shows that warmer temperatures often decrease the extrinsic incubation period of an arthropod-borne virus (arbovirus), exposure to cooler temperatures often predisposes disease vector mosquitoes to higher infection rates. RNA interference (RNAi) pathways are essential to antiviral immunity in the mosquito; however, few experiments have explored the effects of temperature on the RNAi machinery.Methodology/Principal FindingsWe utilized transgenic “sensor” strains of Aedes aegypti to examine the role of temperature on RNA silencing. These “sensor” strains express EGFP only when RNAi is inhibited; for example, after knockdown of the effector proteins Dicer-2 (DCR-2) or Argonaute-2 (AGO-2). We observed an increase in EGFP expression in transgenic sensor mosquitoes reared at 18°C as compared with 28°C. Changes in expression were dependent on the presence of an inverted repeat with homology to a portion of the EGFP sequence, as transgenic strains lacking this sequence, the double stranded RNA (dsRNA) trigger for RNAi, showed no change in EGFP expression when reared at 18°C. Sequencing small RNAs in sensor mosquitoes reared at low temperature revealed normal processing of dsRNA substrates, suggesting the observed deficiency in RNAi occurs downstream of DCR-2. Rearing at cooler temperatures also predisposed mosquitoes to higher levels of infection with both chikungunya and yellow fever viruses.Conclusions/Significance This data suggest that microclimates, such as those present in mosquito breeding sites, as well as more general climactic variables may influence the dynamics of mosquito-borne viral diseases by affecting the antiviral immunity of disease vectors.

Climate, environmental and socio-economic change: weighing up the balance in vector-borne disease transmission

“…Sindbis virus infection and dissemination rates have been found to be higher in Ae. aegypti mosquitoes after rearing larvae at higher temperatures [80], whereas, in contrast, studies have shown increased CHIKV (and YF) infection rates in larvae raised at lower temperatures [71,72].…”

“…Within the flavivirus genus, yellow fever (YF) infection of Aedes aegypti shows a decreased EIP at higher temperatures, but YF infection of Haemagogus mosquitoes demonstrates lower infection rates at lower temperatures [70]. A recent study, however, found increased YF infection in Aedes albopictus mosquitoes reared at lower temperatures (attributable to impaired RNAi responses in the mosquito), demonstrating further the complexities of downstream temperature effects on immature mosquito life stages [71]. Indeed, the same result also appears to be true for chikungunya virus (CHIKV) infection of Ae.…”

“…Indeed, the same result also appears to be true for chikungunya virus (CHIKV) infection of Ae. aegypti [71] and Ae. albopictus [72].…”

Larval Temperature–Food Effects on Adult Mosquito Infection and Vertical Transmission of Dengue-1 Virus

“…Specifically, cooler rearing conditions may compromise the immune system in Ae. albopictus and lead to higher flavivirus and alphavirus infection, perhaps accentuated by nutrient deprivation (Adelman et al 2013). Ae.…”

The role of Culex pipiens mosquitoes in transmission of West Nile virus in Europe

“…Alternatively, temperature may have induced changes in the regulation of biotype-specific immunoresponsive genes, as has been shown for Aedes aegypti mosquitoes infected with chikungunya virus (Mourya et al 2004). In addition, the RNAi pathway becomes more active at higher temperatures and can inhibit viral replication (Adelman et al 2013). Differences in RNAi activity between the biotypes may have resulted in increased sensitivity for WNV infection of biotype pipiens and hybrids at higher temperatures, whereas such changes were not induced in biotype molestus.…”