Scholarly Literature

This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives).  The latest are shown here.
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California Residents’ Perceptions of Gene Drive Systems to Control Mosquito-Borne Disease

20593
C. E. Schairer, C. Triplett, O. S. Akbari and C. S. Bloss,  Frontiers in Bioengineering and Biotechnology,  10. 2022-03-10 11:37:23.
Scientists developing gene drive mosquitoes for vector control must understand how residents of affected areas regard both the problem of mosquito-borne disease and the potential solutions offered by gene drive. This study represents an experiment in public engagement at an early stage of technology development, intended to inform lab scientists about public attitudes toward their research and inspire consideration and conversation about the social ramifications of creating mosquitoes with gene drive. Online focus groups with California residents explored views on mosquito-borne disease risk, current mosquito control methods, and the proposed development and use of different classes of gene drives to control Ae. aegypti. Rather than a dogmatic rejection of genetic engineering or gene drive, many participants expressed pragmatic concerns with cost, control, the ability to narrowly target specific species, and the challenges of mistrust and institutional cooperation. Work like this can inform the alignment of community priorities and the professional priorities of scientists and vector control specialists.

Wolbachia wAlbB inhibits bluetongue and epizootic hemorrhagic fever viruses in Culicoides midge cells

20630
M. L. Matthews, H. O. Covey, B. S. Drolet and C. L. Brelsfoard,  Medical and Veterinary Entomology,  2022-03-10 07:56:14.
Abstract Culicoides midges are hematophagous insects that transmit arboviruses of veterinary importance. These viruses include bluetongue virus (BTV) and epizootic hemorrhagic fever virus (EHDV). The endosymbiont Wolbachia pipientis Hertig spreads rapidly through insect host populations and has been demonstrated to inhibit viral pathogen transmission in multiple mosquito vectors. Here, we have demonstrated a replication inhibitory effect on BTV and EHDV in a Wolbachia (wAlbB strain)-infected Culicoides sonorensis Wirth and Jones W8 cell line. Viral replication was significantly reduced by day 5 for BTV and by day 2 for EHDV as detected by real-time polymerase chain reaction (RT-qPCR) of the non-structural NS3 gene of both viruses. Evaluation of innate cellular immune responses as a cause of the inhibitory effect showed responses associated with BTV but not with EHDV infection. Wolbachia density also did not play a role in the observed pathogen inhibitory effects, and an alternative hypothesis is suggested. Applications of Wolbachia-mediated pathogen interference to impact disease transmission by Culicoides midges are discussed.

No Sting in the Tail for Sterile Bisex Queensland Fruit Fly (Bactrocera tryoni Froggatt) Release Programs

20589
O. L. Reynolds, D. Collins, B. C. Dominiak and T. Osborne,  Insects,  2022-03-09 11:29:49.
Global markets do not tolerate the presence of fruit fly (Tephritidae) in horticultural produce. A key method of control for tephritidae pests, is the sterile insect technique (SIT). Several countries release a bisex strain, i.e., males and females, however the sterile male is the only sex which contributes to wild population declines when released en masse. In commercial orchards, there are concerns that sterile females released as part of bisex strains, may oviposit, i.e., ‘sting’ and cause damage to fruit, rendering it unmarketable. Australia has released a bisex strain of sterile Queensland fruit fly, Bactrocera tryoni Froggatt, for several decades to suppress wild pest populations, particularly in peri-urban and urban environments. Here, we assessed fruit damage in two commercially grown stone fruit orchards where bisex sterile B. tryoni were released, and in an orchard that did not receive sterile flies. The number of detected stings were higher in only one SIT release orchard, compared with the control; however, there was no difference between SIT and control orchards in the number of larvae detected. We showed that there is no evidence that sterile female B. tryoni released in large numbers caused stings, or damage that led to downgraded or unsaleable fruit. The bisex strain of sterile B. tryoni is recommended for use in commercial stone-fruit orchards, under the conditions in which this trial was conducted.

Rescue by gene swamping as a gene drive deployment strategy

20587
K. D. Harris and G. Greenbaum,  bioRxiv,  2022.03.08.483503. 2022-03-08 11:25:49.
Gene drives are genetic constructs that can spread deleterious alleles with potential application to population suppression of harmful species. Given that a gene drive can potentially spill over to other populations or even other species, control measures and fail-safes strategies must be considered. Gene drives are designed to generate a rapid demographic decline, while at the same time generating a dynamic change in the population’s genetics. Since these evolutionary and demographic processes are linked and are expected to occur at a similar time-scale during gene drive spread, feedback between these processes may significantly affect the outcome of deployment. To study this feedback and to understand how it affects gene drive spillovers, we developed a gene drive model that combines evolutionary and demographic dynamics in a two-population setting. The model demonstrates how feedback between evolutionary and demographic dynamics can generate additional outcomes to those generated by the evolutionary dynamics alone. We identify an outcome of particular interest, where the short-term suppression of the target population is followed by gene swamping and loss of the gene drive. This outcome could be useful for designing gene drive deployments that temporarily suppress the population, but ultimately do not remain in the population. Using our model, we demonstrate the robustness of this outcome to spillover and to the evolution of resistance, and suggest that it could be used as a fail-safe strategy for gene drive deployment.Competing Interest StatementThe authors have declared no competing interest.

Selfish migrants: How a meiotic driver is selected to increase dispersal

20575
J. N. Runge, H. Kokko and A. K. Lindholm,  J Evol Biol,  2022-03-07 10:54:44.
Meiotic drivers are selfish genetic elements that manipulate meiosis to increase their transmission to the next generation to the detriment of the rest of the genome. One example is the t haplotype in house mice, which is a naturally occurring meiotic driver with deleterious traits-poor fitness in polyandrous matings and homozygote inviability or infertility-that prevent its fixation. Recently, we discovered and validated a novel effect of t in a long-term field study on free-living wild house mice and with experiments: t-carriers are more likely to disperse. Here, we ask what known traits of the t haplotype can select for a difference in dispersal between t-carriers and wildtype mice. To that end, we built individual-based models with dispersal loci on the t and the homologous wildtype chromosomes. We also allow for density-dependent expression of these loci. The t haplotype consistently evolves to increase the dispersal propensity of its carriers, particularly at high densities. By examining variants of the model that modify different costs caused by t, we show that the increase in dispersal is driven by the deleterious traits of t, disadvantage in polyandrous matings and lethal homozygosity or male sterility. Finally, we show that an increase in driver-carrier dispersal can evolve across a range of values in driver strength and disadvantages.

Gene drives and population persistence vs elimination: The impact of spatial structure and inbreeding at low density

20529
P. J. Beaghton and A. Burt,  Theoretical Population Biology,  2022-03-03 08:28:52.
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.

EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil

20526
M. H. Collins, G. E. Potter, M. D. T. Hitchings, E. Butler, M. Wiles, J. K. Kennedy, S. B. Pinto, A. B. M. Teixeira, A. Casanovas-Massana, N. G. Rouphael, G. A. Deye, C. P. Simmons, L. A. Moreira, M. L. Nogueira, D. A. T. Cummings, A. I. Ko, M. M. Teixeir,  Trials,  23:185. 2022-03-02 08:20:38.
BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.

Increased biting rate and decreased Wolbachia density in irradiated Aedes mosquitoes

20487
R. Moretti, E. Lampazzi, C. Damiani, G. Fabbri, G. Lombardi, C. Pioli, A. Desiderio, A. Serrao and M. Calvitti,  Parasites and Vectors,  15:67. 2022-02-24 08:48:28.
Releasing considerable numbers of radiation-sterilized males is a promising strategy to suppress mosquito vectors. However, releases may also include small percentages of biting females, which translate to non-negligible numbers when releases are large. Currently, the effects of irradiation on host-seeking and host-biting behaviors have not been exhaustively investigated. Information is also lacking regarding the effects of sterilizing treatment on the endosymbiotic bacterium Wolbachia, which is known to affect the vector competence of infected mosquitos.

Regulation of genetically engineered (GE) mosquitoes as a public health tool: a public health ethics analysis

20480
Z. Meghani,  Globalization and Health,  18:21. 2022-02-21 08:33:18.
In recent years, genetically engineered (GE) mosquitoes have been proposed as a public health measure against the high incidence of mosquito-borne diseases among the poor in regions of the global South. While uncertainties as well as risks for humans and ecosystems are entailed by the open-release of GE mosquitoes, a powerful global health governance non-state organization is funding the development of and advocating the use of those bio-technologies as public health tools.

Wolbachia in Aedes koreicus: Rare Detections and Possible Implications

20475
C. Damiani, A. Cappelli, F. Comandatore, F. Montarsi, A. Serrao, A. Michelutti, M. Bertola, M. V. Mancini, I. Ricci, C. Bandi and G. Favia,  Insects,  13. 2022-02-21 08:21:51.
The emerging distribution of new alien mosquito species was recently described in Europe. In addition to the invasion of Aedes albopictus, several studies have focused on monitoring and controlling other invasive Aedes species, as Aedes koreicus and Aedes japonicus. Considering the increasing development of insecticide resistance in Aedes mosquitoes, new control strategies, including the use of bacterial host symbionts, are proposed. However, little is known about the bacterial communities associated with these species, thus the identification of possible candidates for Symbiotic Control is currently limited. The characterization of the natural microbiota of field-collected Ae. koreicus mosquitoes from North-East Italy through PCR screening, identified native infections of Wolbachia in this species that is also largely colonized by Asaia bacteria. Since Asaia and Wolbachia are proposed as novel tools for Symbiotic Control, our study supports their use for innovative control strategies against new invasive species. Although the presence of Asaia was previously characterized in Ae. koreicus, our study characterized this Wolbachia strain, also inferring its phylogenetic position. The co-presence of Wolbachia and Asaia may provide additional information about microbial competition in mosquito, and to select suitable phenotypes for the suppression of pathogen transmission and for the manipulation of host reproduction in Ae. koreicus.

Evaluation of anti-malaria potency of wild and genetically modified Enterobacter cloacae expressing effector proteins in Anopheles stephensi

20485
H. Dehghan, S. H. Mosa-Kazemi, B. Yakhchali, N. Maleki-Ravasan, H. Vatandoost and M. A. Oshaghi,  Parasites and Vectors,  15:63. 2022-02-19 08:43:23.
Malaria is one of the most lethal infectious diseases in tropical and subtropical areas of the world. Paratransgenesis using symbiotic bacteria offers a sustainable and environmentally friendly strategy to combat this disease. In the study reported here, we evaluated the disruption of malaria transmission in the Anopheles stephensi-Plasmodium berghei assemblage using the wild-type (WT) and three modified strains of the insect gut bacterium, Enterobacter cloacae.

Considerations for homology-based DNA repair in mosquitoes: Impact of sequence heterology and donor template source

20478
J. X. D. Ang, K. Nevard, R. Ireland, D.-K. Purusothaman, S. A. N. Verkuijl, L. Shackleford, E. Gonzalez, M. A. E. Anderson and L. Alphey,  PLOS Genetics,  18:e1010060. 2022-02-18 08:29:29.
Author summary The field of genetic control of mosquito vectors has progressed rapidly in recent years, especially in Cas9-based control systems, due to its robustness to elicit a species-specific and dispersive control of mosquito population. To generate a Cas9-based integration, Cas9 and sgRNA are used to cleave a chromosomal locus while a plasmid DNA donor, containing a genetic cargo flanked by sequences homologous to the chromosomal locus, is supplied as a repair template. This results in the cargo being copied into the genome through HDR. This form of integration, however, is currently one of the major bottlenecks for researchers as it involves a laborious process of microinjecting mosquito embryos and has rather low integration rates. In this study, we assessed the effects of homologous sequence mismatches and various donor template forms (i.e. plasmid, ssDNA, biotinylated ds/ssDNA) on HDR. We found that sequence mismatches and non-plasmid donors reduced the efficiency and integrity of integration, respectively. By analysing the direction and length of homologous sequence that was copied into the genome concurrently with the cargo, we inferred the mechanism responsible for the integrations observed in our study. These findings will be useful to guide future construct designs for optimal HDR rates in mosquitoes.

Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development

20447
A. Hoermann, T. Habtewold, P. Selvaraj, G. Del Corsano, P. Capriotti, M. G. Inghilterra, K. M. Temesgen, G. K. Christophides and N. Windbichler,  bioRxiv,  2022.02.15.480588. 2022-02-17 09:41:11.
Gene drives hold promise for the genetic control of malaria vectors. The development of vector population modification strategies hinges on the availability of effector mechanisms impeding parasite development in transgenic mosquitoes. We augmented a midgut gene of the malaria mosquito Anopheles gambiae to secrete two exogenous antimicrobial peptides, Magainin 2 and Melittin. This small genetic modification, capable of efficient non-autonomous gene drive, hampers oocyst development in both Plasmodium falciparum and Plasmodium berghei. It delays the release of infectious sporozoites while it simultaneously reduces the lifespan of homozygous female transgenic mosquitoes. Modeling the spread of this modification using a large-scale agent-based model of malaria epidemiology reveals that it can break the cycle of disease transmission across a range of endemic settings.Competing Interest StatementThe authors have declared no competing interest.

An Ethical Overview of the CRISPR-Based Elimination of Anopheles gambiae to Combat Malaria

20442
I. J. Wise and P. Borry,  Journal of Bioethical Inquiry,  2022-02-17 09:30:10.
Approximately a quarter of a billion people around the world suffer from malaria each year. Most cases are located in sub-Saharan Africa where Anopheles gambiae mosquitoes are the principal vectors of this public health problem. With the use of CRISPR-based gene drives, the population of mosquitoes can be modified, eventually causing their extinction. First, we discuss the moral status of the organism and argue that using genetically modified mosquitoes to combat malaria should not be abandoned based on some moral value of A. gambiae. Secondly, we argue that environmental impact studies should be performed to obtain an accurate account of the possible effects of a potential eradication of the organism. However, the risks from the purposeful extinction of A. gambiae should not overtake the benefits of eradicating malaria and risk assessments should be used to determine acceptable risks. Thirdly, we argue that the eventual release of the genetically modified mosquitoes will depend on transparency, community involvement, and cooperation between different nations.

A-to-I mRNA editing controls spore death induced by a fungal meiotic drive gene in homologous and heterologous expression systems

20415
J. M. Lohmar, N. A. Rhoades, T. N. Patel, R. H. Proctor, T. M. Hammond and D. W. Brown,  Genetics,  2022-02-16 16:59:28.
Spore killers are meiotic drive elements that can block development of sexual spores in fungi. In the maize ear rot and mycotoxin-producing fungus Fusarium verticillioides, a spore killer called SkK has been mapped to a 102-kb interval of chromosome V. Here, we show that a gene within this interval, SKC1, is required for SkK-mediated spore killing and meiotic drive. We also demonstrate that SKC1 is associated with at least four transcripts, two sense (sense-SKC1a and sense-SKC1b) and two antisense (antisense-SKC1a and antisense-SKC1b). Both antisense SKC1 transcripts lack obvious protein-coding sequences and thus appear to be non-coding RNAs. In contrast, sense-SKC1a is a protein-coding transcript that undergoes A-to-I editing to sense-SKC1b in sexual tissue. Translation of sense-SKC1a produces a 70 amino acid protein (Skc1a), whereas translation of sense-SKC1b produces an 84 amino acid protein (Skc1b). Heterologous expression analysis of SKC1 transcripts shows that sense-SKC1a also undergoes A-to-I editing to sense-SKC1b during the Neurospora crassa sexual cycle. Site directed mutagenesis studies indicate that Skc1b is responsible for spore killing in F. verticillioides and that it induces most meiotic cells to die in N. crassa. Finally, we report that SKC1 homologs are present in over 20 Fusarium species. Overall, our results demonstrate that fungal meiotic drive elements like SKC1 can influence the outcome of meiosis by hijacking a cell's A-to-I editing machinery and that the involvement of A-to-I editing in a fungal meiotic drive system does not preclude its horizontal transfer to a distantly related species.

A preliminary framework for understanding the governance of novel environmental technologies: Ambiguity, indeterminateness and drift

20412
F. Rabitz, M. Feist, M. Honegger, J. Horton, S. Jinnah and J. Reynolds,  Earth System Governance,  12:100134. 2022-02-16 16:13:59.
We propose a conceptual framework to explain why some technologies are more difficult to govern than others in global environmental governance. We start from the observation that some technologies pose transboundary environmental risks, some provide capacities for managing such risks, and some do both. For “ambiguous” technologies, potential risks and risk management capacities are uncertain, unknown or even unknowable. Governance systems are indeterminate towards ambiguous technologies, as existing norms, rules, scripts and routines do not imply default solutions under institutional focal points. Indeterminateness can lead to institutional drift, with risks accordingly remaining unmitigated and risk management capacities remaining unexploited. We use the cases of solar geoengineering, gene drive systems and bioinformatics for illustrating this framework. As technological ambiguity may often be irresolvable, we conclude that it might force us to confront the limits to anticipatory global decision-making on matters of long-term environmental sustainability.

Hoisted with his own petard: how sex-ratio meiotic drive in Drosophila affnis creates resistance alleles that limit its spread

20440
W.-J. Ma, K. B. Patch, E. M. Knoles, M. M. Shoaib and R. L. Unckless,  bioRxiv,  2022.02.14.480432. 2022-02-16 09:24:56.
Meiotic drivers are selfish genetic elements that tinker with gameto-genesis to bias their own transmission into the next generation of off-spring. Such tinkering can have significant consequences on gameto-genesis and end up hampering the spread of the driver. In Drosophila affrnis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are more than 95% female. Interestingly, D. affrnis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons - effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 50X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.Competing Interest StatementThe authors have declared no competing interest.

Wolbachia Impacts Anaplasma Infection in Ixodes scapularis Tick Cells

20436
K. M. Skinner, J. Underwood, A. Ghosh, A. S. Oliva Chavez and C. L. Brelsfoard,  International Journal of Environmental Research and Public Health,  19. 2022-02-16 08:58:32.
The specific interactions of members of tick bacterial microbiota and their effects on pathogen transmission remains relatively unexplored. Here, we introduced a novel Wolbachia infection type into Ixodes scapularis tick cells and examined the antipathogenic effects on the intracellular pathogen Anaplasma phagocytophilum. An increase in A. phagocytophilum replication was observed in Wolbachia-infected tick cells. However, Wolbachia infection densities decreased when cells were serially passaged and ultimately the infection was lost. Host-cell immune response was also examined as an additional factor that could have affected A. phagocytophilum replication in Wolbachia-infected cells. In early passages post-Wolbachia infection, a decreased immune response was observed, but in later passages of cells with low Wolbachia densities, there was no change in the immune response. The results are discussed in relation to the importance of studying the interactions of the tick microbiota, the host cell, and the pathogen and the development of novel tick and tick-borne disease-control approaches.

A Closing Window of Opportunity for Gene Drive Governance in the United States

20445
K. L. Warmbrod, M. Montague and G. K. Gronvall,  Health Security,  20:3-5. 2022-02-15 09:35:05.
The COVID-19 pandemic has brought forth a number of biotechnological advances to enhance the public's health: new diagnostic tests, mRNA vaccines, and new antiviral medications. Biotechnology is also being used to address global challenges like climate change, food insecurity, and building the bioeconomy, which directly or indirectly improve public health. Gene drives are one such biotechnology. They are genetically engineered systems that can alter the inheritance patterns in a host species, such as a mosquito, so that a greater percentage of its progeny inherit a specific desired trait. Research and investments in biotechnology have been used to reduce arthropod-borne infectious diseases, such as malaria and Zika, and to manage or eliminate invasive species.2 Funding thus far has been adequate. For example, Target Malaria, a global consortium of researchers developing a gene drive to decrease the burden of malaria, has an average of US$11.5 million per year in funding.3 Although no gene drive has been released into the environment yet, technologies with similar attributes have been released in field trials, notably by Oxitec in Florida

Uniqueness and stability of periodic solutions for an interactive wild and Wolbachia-infected male mosquito model

20438
R. Yan and Q. Sun,  Journal of Biological Dynamics,  2022-02-15 09:03:48.
We investigate a mosquito population suppression model, which includes the release of Wolbachia-infected males causing incomplete cytoplasmic incompatibility (CI). The model consists of two sub-equations by considering the density-dependent birth rate of wild mosquitoes. By assuming the release waiting period T is larger than the sexual lifespan T¯ of Wolbachia-infected males, we derive four thresholds: the CI intensity threshold sh∗, the release amount thresholds g∗ and c∗, and the waiting period threshold T∗. From a biological view, we assume sh > sh∗ throughout the paper. When g∗ < c < c∗, we prove the origin E0 is locally asymptotically stable iff T < T∗, and the model admits a unique T-periodic solution iff T ≥ T∗, which is globally asymptotically stable. When c ≥ c∗, we show the origin E0 is globally asymptotically stable iff T ≤ T∗, and the model has a unique T-periodic solution iff T > T∗, which is globally asymptotically stable. Our theoretical results are confirmed by numerical simulations.

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