Journal of Mosquito Research 2024, Vol.14, No.3, 135-146 http://emtoscipublisher.com/index.php/jmr 137 Ballista et al. (2023) shows the transmission cycle of Chifu encephalitis virus (CHIKV) between mosquitoes and humans. From the perspective of "pathway into mosquito cells", the process begins with the mosquito transmitting the virus into the human body through blood sucking. In the mosquito, CHIKV first infects midgut cells, and then the virus enters other tissues through the blood and eventually reaches the salivary glands. At this point, when the mosquito sucks blood again, the virus enters the new host through the saliva. This process shows the key role of mosquitoes in the virus life cycle, especially the "bridge" role they play in the process of virus entry and transmission. 2.3 Host receptors and entry facilitation Host receptors are crucial for facilitating the entry of pathogens into mosquito cells. The interaction between mosquito receptors and pathogen ligands is a key determinant of successful infection. For example, the Anopheles gambiae odorant binding protein (AgamOBP1) has been shown to mediate the recognition of specific ligands, which could potentially influence pathogen entry. The molecular discrimination of mosquito vectors and their pathogens has advanced our understanding of the specific interactions that facilitate pathogen entry and transmission. The evolutionary dynamics of immune-related genes in mosquitoes also reflect continuous adaptation to pathogen pressures, further influencing the efficiency of pathogen entry (Caluwé et al., 2020). 3 Pathogen Survival and Replication within Mosquito Vectors 3.1 Mechanisms of immune evasion Pathogens have developed sophisticated strategies to evade the immune responses of mosquito vectors. For instance, Plasmodium falciparum, the causative agent of malaria, employs the Pfs47 gene to inhibit Janus kinase-mediated activation, thereby evading the mosquito's immune response (Belachew et al., 2018). Additionally, the pathogen can manipulate host complement factors to protect extracellular gametes in the mosquito midgut from immune attacks (Belachew et al., 2018). Similarly, dengue virus (DENV) exploits the RNA interference (RNAi) mechanism of mosquitoes by recruiting the double-stranded RNA binding protein Loquacious (Loqs) to facilitate its own RNA replication, thus evading the mosquito's antiviral responses (Besson et al., 2022). These evasion strategies are crucial for the pathogens to establish infection and ensure their survival within the mosquito host. 3.2 Intracellular replication strategies Intracellular replication is a common strategy employed by pathogens to avoid detection and destruction by the host immune system. For example, DENV utilizes host proteins such as Loquacious to enhance its replication within mosquito cells. Loquacious colocalizes with DENV double-stranded RNA in viral replication organelles, directly interacting with the viral RNA to facilitate replication (Besson et al., 2022). Similarly, microsporidian pathogens like Edhazardia aedis and Vavraia culicis exhibit distinct replication strategies. E. aedis dynamically upregulates protein trafficking and secretion during infection, while V. culicis focuses on growth and replication, retaining a subset of spliceosomal components to support its intracellular lifestyle. These strategies enable pathogens to efficiently replicate within mosquito cells, ensuring their propagation and transmission. 3.3 Nutrient acquisition and utilization Pathogens must acquire and utilize nutrients from their mosquito hosts to support their growth and replication. The gut microbiota plays a significant role in this process by modulating the mosquito's immune response and nutrient availability (Figure 2). For instance, the gut microbiota can influence the outcomes of infections with malaria parasites in Anopheles mosquitoes by affecting the host's immune responses and nutrient acquisition (Yordanova et al., 2018). Additionally, the interaction between the gut microbiota and mosquito immune system can shape vector competence, impacting the pathogen's ability to acquire and utilize nutrients (Gabrieli et al., 2021). Understanding these interactions is crucial for developing targeted strategies to control mosquito-borne diseases.
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