Temperature plays a vital role in the development and survival of Aedes mosquitoes. The optimal temperature range for their development is 25°C-30°C. When the temperature exceeds 40°C, adult mosquitoes die, and eggs and larvae fail to develop (Reiskind and Zarrabi, 2012). Additionally, both Ae.albopictus and Ae.aegypti larvae are unable to development at 10°C (Reiskind and Zarrabi, 2012; Marinho et al., 2016). Ae.albopictus adults do not feed on blood, while the eggs and larvae need a minimum temperature of 15°C for development (Reiskind and Zarrabi, 2012).

At moderate temperature (20°C-30°C), temperature does no significantly affect the survival of Aedes mosquitoes (Alto and Bettinardi, 2013).Regardless of the rearing temperature of the larvae, the survival rate of adult mosquitoes is significantly higher at 20°C compared to other temperatures (Alto and Bettinardi, 2013). Generally, an increasing temperature is accompanied by an increased activities in Aedes mosquitoes, but excessively high temperatures can shorten their lifespan and reduce their population size (Myer et al., 2020). Females Ae.albopictus tend to survive longer than males at different temperatures. As the temperature rises, the life cycle of Ae. albopictus shortens, and the population growth rate increases (Reiskind and Zarrabi, 2012). Ae.aegypti exhibits a greater tolerate to temperature variations than Ae. albopictus, which provides a competitive advantage (Myer et al., 2020). Ae.aegypti struggles to survive at extremely high or low temperatures, such as below 11°C or above 36°C (Iwamura et al., 2020). Ae.aegypti is less mobile and unable to feed on blood below 14°C-15°C, leading to its mortality. It also cannot survive for more than 2-3 days without a blood meal at tropical temperature (Alto and Bettinardi, 2013).

Temperature affects characteristics of adult Aedes mosquitoes. During the developmental stage, changes in rearing temperature affect the external traits, such as the wing length and the adult size. Higher temperatures(24°C-29°C) and sufficient food are beneficial to mosquito’s ingestion, resulting in shorter wings and heavier weight in Aedes mosquitoes. In contrast, lower temperatures(14°C-19°C) and insufficient food lead to mosquitoes with longer wings and lower weight (Reiskind and Zarrabi, 2012; Alto and Bettinardi, 2013).

Temperature also affects the reproduction activity of Aedes mosquitoes. For example, in areas with an average annual temperature of 22°C, the weekly production of Aedes mosquito eggs is high when the Daily Mean Temperature Range(DTR)ranges from 12°C to 18°C, but it decreases when the temperature exceeds 18°C (Betanzos-Reyes et al., 2018). Extreme temperature like more than 36°C could greatly reduce the number of eggs production (Marinho et al., 2016).

Ae.albopictus is native to Southeast Asia and has recently expanded its range to Africa, where it was first reported in 1990 in South Africa (Cornel and Hunt, 1991). Over the past decade, Ae.albopictus had spread to several Central African countries (Paupy et al., 2009). It rapidly pullulated in Nigeria in 1991 (Savage et al., 1992) and appeared in Central Africa in 2000 (Kamgang et al., 2010).

Temperature exerts an influence on the distribution of Ae.albopictus. It became active when the temperature rises above 13°C, and its population gradually increases following the risen temperature. When the temperature exceeds 36°C, the population began to decline. Ae. albopictus is present in most Asian cities and large parts of the America (Kraemer et al., 2015). For example, in Brownsville, Texas, Ae. albopictus populations generally increases before March and after August, reaching its peak in winter and decreasing in spring and summer (Brady et al., 2014). Ae. albopictus is well adapted to northern South America, where diurnal temperature fluctuates significantly (Brady et al., 2014). In Portugal, Ae.albopictus becomes active in May, with an average minimum temperature of over 13°C and an average maximum temperature of 26.2°C. The peak abundance of Ae. albopictus populations occurs between September and November (average temperatures around 23°C) (Osorio et al., 2020). In China, Ae.albopictus can be found in the southern, eastern, and central regions, and even in some parts of northeastern China. Compared to Ae.aegypti, Ae.albopictus is more adaptable to diurnal and seasonal temperature differences. As temperature increases in the future, Ae.albopictus populations will increase in the central and northern regions, where diurnal temperature differences are more remarkable. Additionally, the warmer south will continue to provide a suitable habitat for Ae.albopictus (Liu B et al., 2019).

Ae.aegypti was originally believed to have originate from Africa (Brown et al., 2014). In 2000, indigenous mosquito species Ae.aegypti were found in Central Africa (Kamgang et al., 2010). Moreover, a study noted that Ae. aegypti can survive in cold winter and will probably spread to colder areas driven by climate change(Kramer et al., 2021).

The distribution of Ae.aegypti is strongly influenced by temperature (Dickens et al., 2018).There is a positive correlation between Ae.aegypti populations and minimum temperatures (Li et al., 2019). Areas with higher minimum temperature (>8°C) are more favorable for the survival of Ae.aegypti (Dickens et al., 2018). When the minimum temperature ranges between 16°C and 20°C, mosquito populations are larger than the average. However, when the minimum temperature exceeds 20°C, Ae.aegypti populations are not affected by further temperature changes. Adults Ae.aegypti populations display a seasonal pattern, with low densities in winter and high densities in summer (Li et al., 2019). Due to their temperature dependence tropical and subtropical areas are their main distribution areas. The temperature differences between day and night are low in Portugal, Spain, southern France, and coastal Italy, which are favorable for the survival of Ae. Aegypti (Dickens et al., 2018). In China, the habitat of Ae. aegypti is confined to specific regions with an annual mean temperature above 20°C, such as Hainan Province, southern Guangdong Province, southern Yunnan Province, et al. When temperatures rise above 35°C, the habitat of Ae. aegypti is adversely affected (Liu B et al., 2019). The abundance of Ae. aegypti gradually increased in all regions from July to October, with a peak in August (Liu B et al., 2019).

DENV belongs to Flaviviridae family of flavivirus. Based on antigenicity difference DENV can be divided into four serotypes(DENV-1, DENV-2, DENV-3, DENV-4) (Sharma et al., 2019). Cross-antigenicity exists among different types of DENV. The structure of DENV-2 is similar to DENV-1 and DENV-3, but exhibits lower similarity with DENV-4 (Lok et al., 2008). DENV is single positive-stranded RNA virus, which encodes three structural proteins and seven nonstructural proteins. The structural proteins include the capsid (C), membrane (M) and envelope (E) protein. The E protein which forms ninety dimers on the surface of mature DENV, plays a significant role in the process of pathogenicity and immunity (Lim et al., 2017a; Boigard et al., 2018; Sharma et al., 2019). The E protein consists of three domains, E-DI [residues 1-52; 132-193; 280-296], E-DII [residues 53-131; 194-279] and E-DIII [residues 297-394]. D-III demonstrates variability of different serotypes as the site of initial interaction with cellular receptors (Slon et al., 2017; Sharma et al., 2019). The seven nonstructural proteins involve NS1\NS2a\NS2b\NS3\NS4a\NS4b\NS5, are involved in viral replication, protein processing, and the assembly and release of viral particles (Boigard et al., 2018).

Temperature mainly affects the structure of the E protein, thereby impacting the overall structure of DENV (Lim et al., 2017b). DENV-2 displays a smooth surface at 28°C, and 96% of them became bumpy at 37°C. The temperature-induced structural alterations usually occurred between 31°C and 35°C and are irreversible, as no structural change are observed when the temperature is lowered from 37°C to 4°C (Zhang et al., 2013). The soluble recombinant E (sRecE) protein is similar to the conformation of E dimers displacing on the virion surface. The sRecE protein of DENV-2, DENV-3 and DENV-4 was in equilibrium between dimer and monomer. At 23°C, sRecE of DENV-2 exists as a dimer, while that of DENV-3 and DENV-4 exists as monomers. At 37°C, sRecE of DENV-2, DENV-3, and DENV-4 mainly exists as monomer (Kudlacek et al., 2018). Another study also demonstrated that the structure of E protein of DENV-2 is irreversible from 40°C to 25°C., with a 50-fold decrease in the ability to form E-dimers at 40°C comparing to 25°C (Sharma et al., 2019). Therefore, the weakened ability of E protein to form dimers may be responsible for the irreversible structural alteration of DENV-2. On the contrary, the structural changes of E protein in DENV-1 are reversible (Sharma et al., 2019).

Virulence of DENV is independent of structural transition but is correlated with intrinsic dynamics. When BHK21 cells were infected with DENV-2, the number of plaque declined by 3-fold at 40°C compared to 25°C and 37°C. Such decrease was caused by the flexibility loss in E-DIII of DENV-2 rather than the structural changes. The flexibility loss in E-DIII of DENV-2 may inhibit the interaction between E-DIII and host cells, thereby further reducing viral infectivity (Sharma et al., 2019). In C6/36 cells infected with DENV-2, the titer of viral particles at 37°C was higher than that at 28°C (Pandey et al., 1998). In AG129 mice infected with DENV-2 incubated at different temperatures has many differences. The mice infected DENV-2 incubated at 39°C died more rapidly than incubated at 28°C.The former have more serious organ injures (Modak et al., 2023).

Vector competence is the ability of mosquitoes to become infected with pathogens and then transmit them to new hosts (Souza-Neto et al., 2019). Various biological and environmental factors could affect vector competence in mosquitoes. Biological factors include mosquito species and strains of virus, while environmental factors include climate, water sources and insecticides (Lounibos and Kramer, 2016; Michael, 2018; Ruckert and Ebel, 2018; Ingham et al., 2021).

The interaction between viruses and mosquitoes is a multi-factorial phenomena, which is determined by both virus strains and mosquito genotypes. MOYO-S and MOYO-R were two groups of Ae.aegypti. MOYO-R was difficult to treat dengue infection, while MOYO-S was susceptible. A large number of genes were differentially expressed between MOYO-S (susceptible) and MOYO-R (refractory) strains of Ae.aegypti infected with DENV-2. The results suggested that susceptibility to DENV-2 is associated with structural/evolutionary features of the responsive genes in MOYO-S/MOYO-R strains (Behura and Severson, 2012). The vector competence of Aedes mosquitoes may vary depending on the virus strain. For instance, the Southeast Asian genotype (SEA strain) of DENV-2 could spread faster than the American genotype (AM strain) (Anderson and Rico-Hesse, 2006). Additionally, the vector competence of Aedes mosquitoes is related to the viral titer in blood meal, with a higher titer facilitating virus transmission (Van den Eynde et al., 2022).

Temperature plays a significant impact on the vector competence of Aedes mosquitoes. Optimal temperatures for DENV transmission are typically between 20°C and 26°C (Ciota et al., 2018). Temperature affects various aspects of mosquito biology, including egg hatching rates, larval developmental time, and adult survival rates, which, in turn, influence vector competence. When survival rate increased from 0.80 to 0.95, the number of potential transmissions increased fivefold. An increase in temperature of 10°C led to a halving of the bite interval and increased transmission by at least 2.4-fold (Barbazan et al., 2010). The rearing environment of mosquito larvae also affects vector competence, as the presence of diverse microorganisms in the breeding water could affect the ability of Ae.aegypti to transmit virus (Louie and Coffey, 2021). Adult female Aedes mosquitoes acquire nutrients from nectar and carbohydrates in the blood, which mainly derived from sugars, including sucrose, fructose and glucose (Elina and Matthew, 2020). The sugar diet of Aedes mosquitoes may reduce their vector competence. Sugar intake could increase the expression of antiviral genes in the digestive tract of female mosquitoes, thereby blocking the initial infection and dissemination of viruses (Almire et al., 2021). In addition, vector control is the most effective and economical method to prevent and control mosquito-borne diseases by reducing the vector competence of mosquitoes through direct killing (Ingham et al., 2021).

Vector competence of mosquitoes is closely associated with immune pathways and tissue barriers (Gloria-Soria et al., 2017). The immune pathways in mosquitoes primarily include RNA interference (RNAi), Toll, immune deficiency(IMD), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) (Liu et al., 2018; Lan et al., 2022). Additionally, Phenoloxidase (PO) plays a crucial role in insect immunity as a key enzyme for melaninization, which is responsible for mosquitoes’ defense against pathogens (Liu et al., 2018; Ji et al., 2022). Arboviruses must overcome several barriers in mosquitoes, including the midgut infection barrier (MIB), midgut escape barrier (MEB), salivary gland infection barrier (SGIB), and salivary gland escape barrier (SGEB) (Franz et al., 2015). The midgut acts as the initial barrier to prevent virus transmission, and the mosquito’s immune system begins to suppress the virus in this region (Liu et al., 2018).

The vector competence of Ae. Albopictus is generally lower than that of Ae. aegypti. However, Ae.albopictus become a main vector for the transmission of DENV in certain regions due to its widespread distribution. When the temperature falls below 18°C, Ae.albopictus does not transmit DENV but can transmit chikungunya virus (Wimalasiri-Yapa et al., 2019). The ability of Ae.albopictus to transmit DENV increased as the temperature risen between 18°C and 32°C. However, when the temperature exceeded 32°C, the mortality rate of Ae.albopictus increased, potentially reducing its vector competence (Liu et al., 2017).

The mechanism by which temperature affects the vector competence of Ae. albopictus had not been fully clarified. Studies suggest that higher temperatures shorten the gonotrophic cycle and led to frequent blood feedings, thereby increasing mosquito’s vector competence (Martens et al., 1995). Temperature also affects the virus to across the midgut barrier. DENV-2 was localized to the midgut of Ae.albopictus and slowly proliferated at 18°C. However, DENV-2 broke through the midgut barrier and invaded the salivary glands of Ae.albopictus between 23°C and 32°C (Liu et al., 2017). The RNAi pathway, Toll pathway, and IMD pathway of the midgut in Ae. albopictus were enhanced at 28°C. The key genes regulated by temperature included heat shock protein 70(HSP70), CCR4-NOT complex, and Myeloid differentiation primary response protein 88 (MyD88) (Liu et al., 2022). HSP70 was the most critical component for DENV-4 entering C6/36 cells (Vega-Almeida et al., 2013). The mRNA expression in the HSP70 was regulated upwards at 37°C and downwards at 39°C (Sivan et al., 2017). The expression level of CCR4-NOT complex gene was upregulated in DENV-2 infected cells, which was conducive to the proliferation of DENV. At 32°C, the CCR4-NOT complex gene is highly expressed in DENV-2 infected cells, facilitating the proliferation of DENV-2 and its ability to break through the midgut barrier (Liu J et al., 2019). However, further functional validation of these key factors is needed in the future ( Figure 1 ).

Ae.aegypti could transmit DENV between temperatures of 22°C and 32°C, but it couldn’t survive when the temperatures rose to about 40°C (Marinho et al., 2016). High mortality rates of mosquitoes inhibited the spread of DENV, thereby reducing their vector competence (Chepkorir et al., 2014). Significant temperature differences between day and night could influence the vector competence of Ae.aegypti by changing vector vital signs and shortening lifespan, which in turn reduced the midgut infection rate and transmission rate for DENV-1 and DENV-2 (Lambrechts et al., 2011). It is worth noting that the impact of temperature fluctuations on vector competence differs based on average temperature levels. At lower average temperatures (<18°C), a temperature fluctuation of 6.26°C between day and night increased the ability of Ae.aegypti to infect and transmit DENV-1. However, at higher average temperatures (≥18°C), the same temperature fluctuation between day and night reduced the vector competence of Ae. Aegypti (Carrington et al., 2013).

The mechanism that how temperature affects the transmission of DENV by Ae. aegypti has not been fully elucidated. The RNAi pathway of Ae.aegypti was compromised at low temperatures, making mosquitoes from warmer regions more susceptible to virus at cold temperatures compared to those from colder regions (Gloria-Soria et al., 2017). Moreover, the impairment of the RNAi pathway in Ae. aegypti increased DENV-2 titers in the midgut, facilitating the dissemination of viruses to other tissues and shortening the EIP (Franz et al., 2015). Ae. aegypti infected with DENV-2 is regulated by the siRNA pathway. It can accelerate DENV replication and shorten EIP by silencing of Dcr 2 or Ago 2 (Sanchez-Vargas et al., 2009). Additionally, Ae.aegypti activated γ-aminobutyric acid (GABA) associated system through blood feeding, enhancing the DENV-2 replication by inhibiting the IMD pathway (Luplertlop et al., 2011). ( Figure 2 )

We refer to other flaviviruses such as Zika virus (ZIKV) and chikungunya virus to indirectly reflect the possible mechanism that how temperature affects the transmission of DENV by Ae.aegypti. The immune reaction of Ae. aegypti infection with the virus could be divided into four components: recognition of pathogen, activation of signal pathway, immune response and immune regulation (Etebari et al., 2017). The recognition of the pathogen was depended on pattern recognition receptors (PRRs) (Julián, 2016), including the clip-domain serine proteases (CLIPs) family B(Wang and Wang et al., 2021), the leucine-rich repeats protein(LRR) (Zhao et al., 2019), thioester-containing protein (TEP) (Weng et al., 2021), and galectins (Xiaohua et al., 2020). The immune response of Ae. aegypti infected with ZIKV was strongest at 28°C, as evidenced by upregulated Dicer-2 activity and the strengthened immune pathways including the Toll pathway, IMD pathway, and JAK/STAT pathway. However, these immune response weakened at 32°C (WimalasiriYapa et al., 2021). Melaninization, which plays a role in the Aedes mosquitoes’ defense against viral infections, is affected by temperature. At 20°C, phenoloxidase and C-type lectin were upregulated in the midgut of Ae. aegypti, reducing its vector competence to transmit ZIKV (Murdock et al., 2012).

The temperature could affect the vector competence of mosquitoes through altering their metabolism. The biochemical activity of mosquitoes was impaired at low temperatures, resulting in the accumulation of fat and reduced energy reserves (Angilletta et al., 2010). The digestion of blood meal in the Ae.aegypti is slow under low temperature. Zinc carboxypeptidase involved in blood meal digestion was significantly downregulated at 20°C to form a peritrophic membrane (PM), which could protect the midgut against pathogens (Ferreira et al., 2020). Additionally, the protein G12 involved in blood meal digestion and nitrile-specific detoxification was increased at 20°C. β-galactosidase and α-N-acetylgalactosaminidase are two digestive proteases involved in glycoside hydrolysis. These highly induced enzymes and proteins contribute to the formation of the PM, slowing down the spread of pathogens and reducing the vector competence of mosquitoes(Santamaria et al., 2015; Ferreira et al., 2020). ( Figure 3 )