Biology subjects

Lau, M.-J.

Publications and source records attributed to Lau, M.-J..

11 recordsLinked to original sources

bioRxiv2023

Jamestown Canyon Virus is transmissible by Aedes aegypti and is only moderately blocked by Wolbachia co-infection

Jamestown Canyon Virus (JCV), a negative-sense arbovirus, is increasingly common in the upper Midwest of the USA. Transmitted by a range of mosquito genera, JCV has at its primary amplifying host, white-tailed deer. Aedes aegypti is the major transmitter globally of the positive-sense viruses dengue (DENV), Zika, chikungunya, and Yellow Fever. Ae. aegyptis distribution, once confined to the tropics, is expanding, in part due to climate change. Wolbachia, an insect endosymbiont, limits the replication of co-infecting viruses inside insects. The release and spread of the symbiont into Ae. aegypti populations has been effective in reducing transmission of dengue and other viruses to humans. The mechanism of Wolbachia-mediated viral blocking in vectors is still poorly understood, however. Here we explored JCV infection potential in Ae. aegypti, the nature of the vectors immune response, and interactions with Wolbachia infection. We show that Ae. aegypti is highly competent for JCV, growing to substantial loads and rapidly reaching the saliva after an infectious blood meal. The mosquito immune system responds with strong induction of RNAi and JAK/STAT. Neither the direct effect of viral infection nor the energetic investment in immunity appears to affect mosquito longevity. Wolbachia infection blocked JCV only in the early stages of infection. Wolbachia-induced immunity was small compared to that of JCV, suggesting innate immune priming does not likely explain blocking. We propose two models to explain why Wolbachias blocking of negative-sense viruses like JCV may be less than that of positive-sense viruses, relating to the slowdown of host protein synthesis and the triggering of interferon-like factors like Vago. In conclusion, we highlight the risk for increased human disease with the predicted future overlap of Ae. aegypti and JCV ranges. We suggest that with moderate Wolbachia-mediated blocking and distinct biology, negative-sense viruses represent a fruitful comparator model to other viruses for understanding blocking mechanisms in mosquitoes. Author SummaryJamestown Canyon Virus (JCV), a newly emerging virus in North America, causes disease when it spills out of its wild mammal hosts into human populations via the bite of infected mosquitoes. We show that the mosquito Aedes aegypti, known for transmitting many viral pathogens to humans globally, and whose distribution is creeping northward in the USA toward regions where JCV is present, is likely able to transmit the virus. Wolbachia is an endosymbiotic bacterium being released in wild mosquito populations of mosquitoes because it limits the replication of human viruses inside the mosquito, limiting their transmission to humans. We show that Wolbachia has a limited ability to control the replication of JCV, which is likely because Wolbachia-induced antiviral response is quite weak, and unique aspects of negative-sense virus biology make them less susceptible to blocking. Our findings suggest that JCV may serve as a comparative model to positive-sense viruses like dengue in dissecting the mechanism of Wolbachia-mediated virus blocking. It also warns that shifting mosquito distributions, as expected under a changing climate, could bring JCV and Aedes mosquitoes into greater contact, potentially increasing the incidence of JCV in humans.

pathology↗

bioRxiv2022

Lipidomic change in Aedes aegypti female following blood feeding reveals similar changes in functionally related lipids

We conducted a lipidomic analysis of the whole body of female Aedes aegypti mosquitoes at different time points over the course of feeding and reproduction. There were temporal biphasic increases of more than 80% of lipids identified at the time of feeding and from 16 h to 30 h post blood meal. During these two increases, the abundance of many lipids dropped while body weight remained stable, probably reflecting blood lipid digestion and the synthesis of vitellogenin in this period. A concerted temporal pattern was particularly strong at the second peak for membrane and signalling lipids such as PE, PI, CL, HexCer and LPA. Lyso-glycerophospholipids showed three distinct change patterns which are functionally related: LPE and LPC, which are membrane lipids, showed little change; LPA, a signalling lipid, showed a dramatic increase from 16 to 30 h PBM; LPI, a bioactive lipid, and both LPG and LPS which are bacterial membrane lipids, showed one significant increase from the time of feeding to 16 hours post blood meal. The result of our study on the anautogenous insect Ae. aegypti point to specific lipids likely to be important in the reproductive process with a role in the formation and growth of ovarian follicles.

biochemistry↗

bioRxiv2022

Wolbachia inhibits ovarian formation and increases blood avidity in female Aedes aegypti-a novel time-specific reproductive alteration

Wolbachia, a gram-negative endosymbiotic bacterium widespread in arthropods, is well-known for changing the reproduction of its host in ways that increase its rate of spread, but there are also costs to hosts that can reduce this. Here we investigated a novel reproductive alteration of Wolbachia wAlbB on its mosquito host Aedes aegypti, based on studies of mosquito life history traits, ovarian dissections and gene expression assays. We found that an extended period of the larval stage as well as the egg stage, as previously shown, can increase the proportion of Wolbachia-infected females that become infertile; the impact of Wolbachia on infertility therefore accumulated before pupation. We found that ovarian formation was blocked in infertile females, even though infected females had relatively lower Wolbachia densities than fertile infected females. Infertile females also showed a higher frequency of blood feeding following a prior blood meal, indicating that they do not enter a complete gonotrophic cycle. Treatments leading to infertility decreased expression of genes related to reproduction. Our results demonstrate effects related to the causes and consequences of infertile wAlbB-infected Ae. aegypti females with implications for Wolbachia releases and have evolutionary implications for Wolbachia infections in novel hosts.

microbiology↗

bioRxiv2022

A wMel Wolbachia variant in Aedes aegypti from field-collected Drosophila melanogaster with increased phenotypic stability under heat stress

Mosquito-borne diseases such as dengue, Zika and chikungunya remain a major cause of morbidity and mortality across tropical regions. Population replacement strategies involving the wMel strain of Wolbachia are being used widely to control mosquito-borne diseases transmitted by Aedes aegypti. However, these strategies may be influenced by environmental temperature because wMel is vulnerable to heat stress. wMel infections in their native host Drosophila melanogaster are genetically diverse, but few transinfections of wMel variants have been generated in Ae. aegypti mosquitoes. Here we successfully transferred a wMel variant (termed wMelM) originating from a field-collected D. melanogaster population from Victoria, Australia into Ae. aegypti. The new wMelM variant (clade I) is genetically distinct from the original wMel transinfection (clade III) generated over ten years ago, and there are no genomic differences between wMelM in its original and transinfected host. We compared wMelM with wMel in its effects on host fitness, temperature tolerance, Wolbachia density, vector competence, cytoplasmic incompatibility and maternal transmission under heat stress in a controlled background. wMelM showed a higher heat tolerance than wMel, with stronger cytoplasmic incompatibility and maternal transmission when eggs were exposed to heat stress, likely due to higher overall densities within the mosquito. Both wMel variants had minimal host fitness costs, complete cytoplasmic incompatibility and maternal transmission, and dengue virus blocking under standard laboratory conditions. Our results highlight phenotypic differences between closely related Wolbachia variants. wMelM shows potential as an alternative strain to wMel in dengue control programs in areas with strong seasonal temperature fluctuations.

microbiology↗

bioRxiv2021

A decade of stability for wMel Wolbachia in natural Aedes aegypti populations

Mosquitoes carrying Wolbachia endosymbionts are being released in many countries for arbovirus control. The wMel strain of Wolbachia blocks Aedes-borne virus transmission and can spread throughout mosquito populations by inducing cytoplasmic incompatibility. Aedes aegypti mosquitoes carrying wMel were first released into the field in Cairns, Australia, over a decade ago, and with wider releases have resulted in the near elimination of local dengue transmission. The long-term stability of Wolbachia effects is critical for ongoing disease suppression, requiring tracking of phenotypic and genomic changes in Wolbachia infections following releases. We used a combination of field surveys, phenotypic assessments, and Wolbachia genome sequencing to show that wMel has remained stable in its effects for up to a decade in Australian Ae. aegypti populations. Phenotypic comparisons of wMel-infected and uninfected mosquitoes from near-field and long-term laboratory populations suggest limited changes in the effects of wMel on mosquito fitness. Treating mosquitoes with antibiotics used to cure the wMel infection had limited effects on fitness in the next generation, supporting the use of tetracycline for generating uninfected mosquitoes without off-target effects. wMel has a temporally stable within-host density and continues to induce complete cytoplasmic incompatibility. A comparison of wMel genomes from pre-release (2010) and nine years post-release (2020) populations show few genomic differences and little divergence between release locations, consistent with the lack of phenotypic changes. These results indicate that releases of Wolbachia-infected mosquitoes for population replacement are likely to be effective for many years, but ongoing monitoring remains important to track potential evolutionary changes. Author summaryWolbachia are endosymbionts that can block the transmission of arboviruses by mosquitoes. Aedes aegypti mosquitoes carrying the wMel strain of Wolbachia have been released in population replacement interventions, which aim to establish wMel in mosquito populations, thereby reducing their ability to spread disease. Wolbachia population replacement programs began only a decade ago, raising uncertainty about their long-term effectiveness. Here we provide a comprehensive assessment of the long-term stability of wMel from the very first Wolbachia population replacement release. We show that there is no evidence for changes in the phenotypic effects of wMel in mosquitoes, and confirm that the wMel genome has changed very little in the decade since field releases began. wMel remains at high levels within mosquitoes, suggesting that its ability to block virus transmission has been retained. Our data provides confidence that Wolbachia population replacement releases will provide ongoing protection against arbovirus transmission.

evolutionary biology↗

bioRxiv2021

Diagnostic primers to distinguish between wMel and wAlbB Wolbachia infection - A simplified approach for use in field-collected Aedes aegypti in dengue reduction trials

Detection of the Wolbachia endosymbiont in Aedes aegypti mosquitoes through real-time PCR assays is widely used during and after Wolbachia releases in dengue reduction trials involving the wMel and wAlbB strains. However, primers applied in current successful Wolbachia releases cannot be used in a single assay to distinguish between these strains. Here, we developed a new diagnostic primer pair wMA which can detect wMel or wAlbB infection in the same assay. We also tested current Wolbachia primers and show that there is variation in their performance when they are used to assess the relative density of Wolbachia. The new wMA primers provide an accurate and efficient estimate of the presence and density of both Wolbachia infections.

microbiology↗

bioRxiv2021

Genetic stability of Aedes aegypti populations following invasion by wMel Wolbachia

BackgroundWolbachia wMel is the most used strain in mosquito rear and release strategies that aim to inhibit the transmission of arboviruses such as dengue, Zika, Chikungunya and yellow fever. However, the long-term establishment of wMel in natural populations of the dengue mosquito Aedes aegypti raises concerns that interactions between Wolbachia wMel and Ae. aegypti may lead to changes in the host genome, which could affect useful attributes of Wolbachia that allow it to invade and suppress disease transmission. ResultsWe applied an evolve-and-resequence approach to study genome-wide genetic changes in Ae. aegypti from the Cairns region, Australia, where Wolbachia wMel was first introduced more than 10 years ago. Mosquito samples were collected at three different time points in Gordonvale, Australia, covering the phase before (2010) and after (2013 and 2018) Wolbachia releases. An additional three locations where Wolbachia replacement happened at different times across the last decade were also sampled in 2018. We found that the genomes of mosquito populations mostly remained stable after Wolbachia release, with population differences tending to reflect the geographic location of the populations rather than Wolbachia infection status. However, outlier analysis suggests that Wolbachia may have had an influence on some genes related to immune response, development, recognition and behavior. ConclusionsAedes aegypti populations remained geographically distinct after Wolbachia releases in North Australia despite their Wolbachia infection status. At some specific genomic loci, we found signs of selection associated with Wolbachia, suggesting potential evolutionary impacts can happen in the future and further monitoring is warranted.

evolutionary biology↗

bioRxiv2021

Strong attraction of male mosquitoes (Aedes aegypti) to humans

Female Aedes aegypti mosquitoes integrate multiple sensory cues to locate human hosts for blood meals. While male mosquitoes do not blood feed, male Ae. aegypti swarm around and land on humans in nature. Basrur et al. (2020) generated male Ae. aegypti lacking the fruitless gene and discovered that they gained strong attraction to humans, similar to female mosquitoes. The authors assume that host-seeking is a female-specific trait. However, all experiments were performed under confined laboratory conditions which are unable to detect long-range attraction. We used semi-field experiments to demonstrate robust attraction of male Ae. aegypti to humans. Our observations refute a key assumption of Basrur et al. (2020) and raise questions around conditions under which fruitless prevents male host-seeking. Male mosquito attraction to humans is likely to be important for mating success in wild populations and its basis should be further explored.

animal behavior and cognition↗

bioRxiv2020

Infertility and fecundity loss of Wolbachia-infected Aedes aegypti hatched from quiescent eggs is expected to alter invasion dynamics

The endosymbiotic bacterium Wolbachia shows viral blockage in its mosquito host, leading to its use in arboviral disease control. Releases with Wolbachia strains wMel and wAlbB infecting Aedes aegypti have taken place in several countries. Mosquito egg survival is a key factor influencing population persistence and this trait is also important when eggs are stored prior to releases. We therefore tested the viability of mosquitoes derived from Wolbachia wMel and wAlbB-infected as well as uninfected eggs after long-term storage under diurnal temperature cycles of 11-19{degrees}C and 22-30{degrees}C. Eggs stored at 11-19{degrees}C had higher hatch proportions than those stored at 22-30{degrees}C. Adult Wolbachia density declined when they emerged from eggs stored for longer, which was associated with incomplete cytoplasmic incompatibility (CI) when wMel-infected males were crossed with uninfected females. wAlbB-infected males continued to show complete CI. Females from stored eggs at both temperatures continued to show perfect maternal transmission of Wolbachia, but storage reduced the fecundity of both wMel and wAlbB-infected females relative to uninfected mosquitoes. Furthermore, we found a very strong negative impact of the wAlbB infection on the fertility of females stored at 22-30{degrees}C, with almost 80% of females hatching after 11 weeks of storage being infertile. Our findings provide guidance for storing Wolbachia-infected Ae. aegypti eggs to ensure high fitness adult mosquitoes for release. Importantly, they also highlight the likely impact of egg quiescence on the population dynamics of Wolbachia-infected populations in the field, and the potential for Wolbachia to suppress mosquito populations through cumulative fitness costs across warm and dry periods, with expected effects on dengue transmission.

evolutionary biology↗

bioRxiv2019

Does membrane feeding compromise the quality of Aedes aegypti mosquitoes?

Modified Aedes aegypti mosquitoes are being mass-reared for release in disease control programs around the world. Releases involving female mosquitoes rely on them being able to seek and feed on human hosts. To facilitate the mass-production of mosquitoes for releases, females are often provided blood through artificial membrane feeders. When reared across generations there is a risk that mosquitoes will adapt to feeding on membranes and lose their ability to feed on human hosts. To test adaptation to membrane feeding, we selected replicate populations of Ae. aegypti for feeding on either human arms or membrane feeders for at least 8 generations. Membrane-selected populations suffered fitness costs, likely due to inbreeding depression arising from bottlenecks. Membrane-selected females had higher feeding rates on membranes than human-selected ones, suggesting adaptation to membrane feeding, but they maintained their attraction to host cues and feeding ability on humans despite a lack of selection for these traits. Host-seeking ability in small laboratory cages did not differ between populations selected on the two blood sources, but membrane-selected females were compromised in a semi-field enclosure where host-seeking was tested over a longer distance. Our findings suggest that Ae. aegypti may adapt to feeding on blood provided artificially, but this will not substantially compromise field performance or affect experimental assessments of mosquito fitness. However, large population sizes during mass rearing with membrane feeders should be maintained to avoid bottlenecks which lead to inbreeding depression.\n\nAuthor summaryWith modified mosquitoes being mass-reared for release in disease control programs, there is interest in understanding factors that can affect the quality of release stocks. In the laboratory, membrane feeding devices are often used to provide blood to female mosquitoes which they need to lay eggs. Over time, mosquitoes could adapt to membrane feeding and lose their preference for (or ability to feed on) natural hosts. Adaptation could affect the performance of lab-reared mosquitoes when deployed in the field, especially if the success of disease control programs relies on female reproduction such as in gene drive or Wolbachia-based approaches. We tested to see if Aedes aegypti mosquitoes, the principal vectors of dengue virus, would adapt to feeding on blood provided via membranes. We found some evidence of adaptation, with membrane-selected mosquitoes having higher feeding rates on membranes, but this didnt affect their ability to feed on humans or their attraction to host cues. Although membrane feeding alone does not substantially affect mosquito quality, it can lead to inbreeding depression if populations pass through bottlenecks as they adapt to feeding on blood provided artificially. Our results may inform mass-rearing programs involving the release of modified female mosquitoes.

evolutionary biology↗

bioRxiv2019

Measuring the host-seeking ability of Aedes aegypti destined for field release

Host-seeking is an essential process in mosquito reproduction. Field releases of modified mosquitoes for population transformation rely on successful host-seeking by female mosquitoes, but host-seeking ability is rarely tested in a realistic context. We tested the host-seeking ability of female Aedes aegypti mosquitoes using a semi-field system. Females with different Wolbachia infection types (wMel-, wAlbB-infected and uninfected) or from different origins (laboratory and field) were released at one end of a semi-field cage and recaptured as they landed on human experimenters fifteen meters away. Mosquitoes from each population were then identified with molecular tools or through marking with a consistent weight of fluorescent powder. Wolbachia-infected and uninfected populations had similar average durations to landing and overall recapture proportions, as did laboratory and field-sourced A. aegypti. These results suggest that the host-seeking ability of mosquitoes is not negatively affected by Wolbachia infection or long-term laboratory maintenance. This method provides an approach to study the host-seeking ability of mosquitoes across a long distance which will be useful when evaluating strains of mosquitoes that are planned for releases into the field to suppress arbovirus transmission. An adjustment of this method may also be useful in sterile insect release programs because male host-seeking and swarming around female feeding sites can also be investigated.

animal behavior and cognition↗