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Culex is a cosmopolitan genus of mosquitoes in the subfamily Culicinae of the family Culicidae. The genus contains roughly 770 recognized species in about 26 subgenera, though the exact numbers differ among taxonomic authorities. Important subgenera include Culex (in the strict sense), Melanoconion, Neoculex, and Barraudius. The group formerly treated as the subgenus Lutzia is regarded as a separate genus by some authors. The genus was established by Carl Linnaeus in the tenth edition of Systema Naturae (1758). Culex species occur in tropical, subtropical, and temperate regions of every continent except Antarctica. Members of the Culex pipiens group are commonly called house mosquitoes.

Together with Aedes and Anopheles, Culex is one of the three mosquito genera of greatest importance in medical entomology and veterinary medicine. Aedes species are the main vectors of dengue, yellow fever, Zika, and chikungunya, and Anopheles species transmit malaria to humans. Culex species, by contrast, mainly maintain and transmit zoonotic arboviruses in cycles involving birds and mammals, and they transmit some filarial nematodes and avian malaria parasites. The principal _Culex_-borne agents include:

• Orthoflaviviruses of the Japanese encephalitis serogroup: West Nile virus (WNV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), Murray Valley encephalitis virus (MVEV), and Usutu virus (USUV).
• Alphaviruses and bunyaviruses: Western equine encephalitis virus (WEEV), enzootic subtypes of Venezuelan equine encephalitis virus (VEEV), Sindbis virus (SINV), and Rift Valley fever virus (RVFV), for which Culex species are secondary vectors that can amplify epidemics begun by Aedes species.
• Parasites: Wuchereria bancrofti, the main cause of lymphatic filariasis, for which Culex quinquefasciatus is the principal urban vector, and Plasmodium relictum, the cause of avian malaria.

Several biological features distinguish Culex from Aedes and shape how its vector species respond to urbanization and climate change. Females lay their eggs as floating rafts on standing, often nutrient-rich water rather than as single drought-resistant eggs. Most vector species feed mainly from dusk to dawn. Many switch seasonally from feeding on birds to feeding on mammals. Temperate species survive the winter as mated adult females in reproductive diapause rather than as eggs.

The genus Culex is the type genus of the tribe Culicini. The subgenera differ greatly in size and geography. Melanoconion is a Neotropical subgenus with well over 150 species, whereas the subgenus Culex is cosmopolitan and contains the most important vectors of human disease, including the Culex pipiens complex, Culex tarsalis, and Culex tritaeniorhynchus.

Morphological differences from Aedes and Anopheles

Each of the four holometabolous life stages (egg, larva, pupa, and adult) has characters that separate Culex from the other two genera in field identification and surveillance.

Egg rafts and oviposition

A gravid Culex female settles on the water surface and holds her hind legs crossed behind the abdomen. She extrudes elongate eggs one at a time and glues them upright and side by side. The finished raft is boat-shaped, buoyant, and hydrophobic, and it measures a few millimeters in length. Because Culex eggs lack the desiccation resistance of many Aedes eggs, they survive only while the raft remains on water. At 25 to 28 °C, embryogenesis takes about 1 to 2 days, and the first-instar larvae leave through the underside of the raft.

Most of the important urban and agricultural vector species, including Cx. pipiens, Cx. quinquefasciatus, and Culex restuans, prefer organically enriched water such as stormwater catch basins, drainage ditches, septic systems, and polluted ponds. Larvae filter-feed on bacteria and protozoa in this water, and they obtain oxygen from the air through the siphon, so low dissolved oxygen does not harm them.

Gravid females locate oviposition sites at night with a combination of cues:

• Volatile products of microbial decomposition, notably indole, 3-methylindole (skatole), _p_-cresol, and phenol, detected by olfactory neurons on the antennae and maxillary palps.
• A conspecific pheromone, (5_R_,6_S_)-6-acetoxy-5-hexadecanolide, released from an apical droplet on each egg. It attracts other gravid females, which leads to clustered oviposition in the same water body.

Larval and pupal development

In Culex species, development time depends strongly on temperature, food supply, and crowding. Under warm conditions the aquatic stages can be completed in about 1 to 2 weeks. Four larval instars precede the non-feeding but active pupal stage. The adult emerges at the surface. Larval nutrition influences adult size, autogeny in some forms, and lipid reserves.

Adult feeding

Both sexes of Culex feed on plant sugars such as nectar and honeydew. Females also require a vertebrate blood meal to develop eggs, except in autogenous populations. Most vector species are active at dusk and at night. Host-seeking relies on carbon dioxide, skin and avian odors such as nonanal, lactic acid, and octenol, and body heat. After a blood meal, the female digests it and matures a batch of eggs during a gonotrophic cycle lasting several days, with the duration depending on temperature.

Seasonal shifts in host use

Studies of blood meals in several temperate Culex species, including Cx. pipiens, Cx. restuans, and Cx. tarsalis, show that they feed mostly on birds in spring and early summer and take a larger share of mammalian blood, including human blood, in late summer and autumn. In Cx. nigripalpus in Florida a similar shift from birds to mammals has been documented.

Feeding on birds is also non-random. In some North American communities, the American robin supplies a share of blood meals several times larger than its share of the local bird community. The shift to mammals has been linked in part to the late-summer dispersal of robins from residential areas. Because infection prevalence in mosquitoes is usually highest in late summer, this shift to humans and horses can contribute to the seasonal peak of human West Nile virus cases. The pattern is not uniform, however. Feeding behavior and its role in epidemics differ among regions and among genetic forms of Cx. pipiens, and the shift can also reflect changes in host availability rather than a change in mosquito preference.

Overwintering and reproductive diapause

In temperate regions, Cx. pipiens (form pipiens), Cx. tarsalis, Cx. restuans, and populations of Cx. tritaeniorhynchus in cooler parts of Asia survive winter as adult females in diapause. Shortening autumn day length and falling temperatures, experienced during larval and pupal development, trigger the program. In the female, the main features of diapause are:

• Suppressed insulin signaling and reduced activity of FOXO regulation pathways, together with shutdown of juvenile hormone synthesis by the corpora allata. As a result, ovarian follicles stop developing at an early previtellogenic stage.
• Loss of host-seeking and blood-feeding behavior.
• Heavy sugar feeding and lipogenesis, so that the fat body expands and supplies energy for months without food. Genes for fatty acid synthase and fatty acid desaturases are upregulated.
• Changes in cuticle composition, stress-response proteins such as heat-shock proteins, and antioxidant enzymes, along with a preference for dark, humid, sheltered sites called hibernacula, such as culverts, cellars, and animal burrows.

Males mate in autumn and die with the first frosts. Females store sperm in the spermathecae until spring. When temperatures rise and day length increases, juvenile hormone synthesis resumes, the female feeds on blood, and she lays her first egg raft. Evidence indicates that WNV can persist through winter in some overwintering females, probably after vertical transmission from an infected mother, although the extent to which this seeds the next season's epizootic remains debated.

Although several hundred Culex species have been described, a limited number account for most disease transmission.

The Culex pipiens complex

The Cx. pipiens complex includes Cx. pipiens, Cx. quinquefasciatus, Culex pallens in East Asia, and the Australian species Culex australicus and Culex globocoxitus. These taxa are morphologically similar and in places hybridize.

Within Cx. pipiens two forms with very different biology coexist:

• Form pipiens lives above ground, mates in open swarms (eurygamy), requires a blood meal for each batch of eggs (anautogeny), feeds mainly on birds, and enters winter diapause.
• Form molestus (described by Peter Forsskål in 1775 from Egypt) is associated with underground and indoor habitats such as basements, sewers, and subway tunnels. It mates in confined spaces (stenogamy), can lay a first batch of eggs without a blood meal (autogeny), feeds readily on mammals including humans, and does not enter diapause. Its association with London Underground shelters during the Blitz made it known as the "London Underground mosquito."

In northern Europe, the two forms are largely isolated by habitat. In North America, genetic studies indicate that Cx. pipiens populations contain a substantial and variable proportion of molestus ancestry, and that Cx. pipiens and Cx. quinquefasciatus hybridize in a zone at middle latitudes of the United States (roughly 36°N to 39°N). Hybrids may feed on both birds and mammals, and this behavior has been proposed as one reason that West Nile virus has caused larger human epidemics in North America than in parts of northern Europe. The hypothesis is supported by some data but is not fully settled.

The genome of Cx. quinquefasciatus was sequenced in 2010, and later assemblies were improved with long-read data. It spans roughly 579 megabases on three chromosomes and encodes about 18,900 protein-coding genes, which is more than the genomes of Aedes aegypti (roughly 15,000 genes) and Anopheles gambiae (roughly 12,500 genes) at the time. Notable lineage-specific expansions include:

• Chemosensory genes: About 180 olfactory receptor genes, among the largest sets known for a mosquito. They are thought to underlie the ability to detect bird and mammal odors as well as microbial odors at oviposition sites.
• Detoxification genes: Families of cytochrome P450 enzymes, glutathione S-transferases, and carboxylesterases, consistent with larval life in polluted water and with the frequent evolution of insecticide resistance.
• Salivary and immune genes: Families of C-type lectins, D7 proteins, and other salivary proteins that affect feeding and host responses.

Humans and horses are usually dead-end hosts for the bird-associated _Culex_-borne viruses, which means they develop too little viremia to infect biting mosquitoes. The viruses are amplified in birds (or, for JEV, in pigs), and human disease arises from spillover by mosquitoes that feed on both birds and mammals.

Oropouche virus, an orthobunyavirus, is transmitted mainly by the biting midge Culicoides paraensis. Cx. quinquefasciatus has been proposed as a secondary vector, but its role is unconfirmed and laboratory competence appears low. Despite early reports, Culex species are generally regarded as poor vectors of dengue, Zika, and chikungunya viruses.

Lymphatic filariasis

Adult W. bancrofti worms live in human lymphatic vessels for about 5 to 8 years and release sheathed microfilariae. In many areas these circulate in peripheral blood mainly at night, which coincides with the biting activity of Cx. quinquefasciatus. After ingestion, microfilariae penetrate the midgut, migrate to the thoracic flight muscles, and molt twice to reach the infective third larval stage in about 10 to 14 days at around 27 °C. The larvae then move to the proboscis. In Culex species, the proportion of microfilariae that develop declines as microfilarial density in the blood rises (limitation), which is the opposite of the facilitation seen in many Anopheles vectors, in which cibarial armature damages ingested microfilariae. About 51 million infections were estimated in 2018, a reduction of roughly three quarters since 2000.

Avian malaria in Hawaii

Cx. quinquefasciatus was introduced to Hawaii in the early nineteenth century, with the first records in 1826 at Lahaina on Maui. Avian malaria followed later, probably in the twentieth century. Native Hawaiian honeycreepers (the Drepanidinae) evolved without these pathogens, and experimental infections kill a large fraction of individuals in susceptible species. Together with habitat loss and introduced predators, avian disease contributed to the extinction or decline of many native forest birds. Surviving populations of several species persist mainly at high elevations above roughly 1,500 m, where cool temperatures limit mosquito development and parasite maturation.

For a virus to be transmitted by Culex, it must infect the midgut, escape into the hemolymph, infect the salivary glands, and be released in saliva. Barriers at each step determine vector competence, which varies among species, populations, and virus genotypes. Examples of molecular determinants include:

• Envelope substitution in WNV: West Nile virus was introduced to New York in 1999. A genotype called WN02, carrying a V159A substitution in the envelope glycoprotein, displaced the original NY99 genotype within a few years. Experiments showed that WN02 is transmitted earlier and more efficiently by Culex mosquitoes because of a shorter extrinsic incubation period, especially at warm temperatures.
• NS1′ protein: Viruses of the Japanese encephalitis serogroup have a conserved slippery sequence and downstream RNA pseudoknot in the NS2A gene region. This induces a programmed −1 ribosomal frameshift in a fraction of translation events and yields an extended form of the NS1 protein called NS1′, which has been implicated in neuroinvasiveness and viral fitness.
• Mosquito proteins that assist infection: A mosquito C-type lectin that binds WNV and a receptor-type tyrosine phosphatase on midgut cells have been shown to promote infection, in work done in Aedes aegypti and confirmed for orthologs in Culex.
• Antiviral immunity: The main antiviral defense is the exogenous small interfering RNA pathway, which depends on Dicer-2 and Argonaute-2. Flaviviral subgenomic RNA (sfRNA) can suppress RNA interference. Other pathways, including the JAK-STAT and Toll pathways, also contribute.
• Symbionts: Most wild Cx. pipiens complex mosquitoes carry the intracellular bacterium Wolbachia pipientis (strain _w_Pip), which causes cytoplasmic incompatibility and may influence susceptibility to some pathogens.

Basic reproduction number and vectorial capacity

For a _Culex_-borne pathogen in a single host species, the basic reproduction number in the classical Ross-Macdonald model is:

where m is the number of mosquitoes per host, a is the daily biting rate, b is the probability that an infectious bite infects a host, c is the probability that a bite on an infectious host infects a mosquito, μ is the daily adult mosquito mortality rate, n is the extrinsic incubation period in days, and r is the host recovery rate. The mosquito-specific portion is the vectorial capacity:

In multi-host systems such as the bird community involved in WNV transmission, the host-dependent terms are summed over host species weighted by the fraction of blood meals each species supplies. Species differ greatly in reservoir competence, which is the product of susceptibility, infectiousness to mosquitoes, and duration of infectious viremia. Passerines such as house finches, house sparrows, and corvids tend to be competent, whereas pigeons, chickens, and most mammals are poor reservoirs and can dilute transmission if mosquitoes feed on them heavily.

The extrinsic incubation period shortens with temperature. Over a limited range it is often approximated by a degree-day relation:

where D is the thermal sum required for virus development, T is temperature, and T_min is the lower threshold for viral development.

Human spillover risk at time t depends on the density of infectious mosquitoes, their biting rate, and the fraction of bites directed at humans, φ_human(t):

where I_v is the fraction of mosquitoes that are infectious. Risk is therefore highest when early-season bird feeding builds up I_v and a later increase in feeding on mammals raises φ_human.

Temperature dependence

Culex mosquito and viral traits respond nonlinearly to temperature, and transmission is typically a unimodal function of temperature. Trait curves such as development rate are often fitted with the Brière function:

where c is a scaling constant and T_min and T_max are the lower and upper thermal limits. Trait-based models for _Culex_-borne viruses estimate that transmission peaks at about 23 to 26 °C. Estimated optima include roughly 24.5 °C for Cx. pipiens with WNV, about 25.2 °C for Cx. quinquefasciatus with WNV, and about 23.9 °C for Cx. tarsalis with WNV. These optima are several degrees cooler than the roughly 29 °C estimated for Aedes aegypti with dengue, Zika, and chikungunya viruses. As a consequence, in the warmest regions further warming may reduce summer transmission, while in cooler regions it extends the transmission season and raises peak risk. Projections therefore anticipate shifts in the seasonality and geography of _Culex_-borne disease rather than a uniform increase.

Interactions between temperature and genetics matter as well. For WEEV, which declined markedly in North America, proposed contributing factors include temperature effects on vector competence in Cx. tarsalis, equine vaccination, changes in irrigation and land use, and changes in surveillance. The relative importance of these factors is uncertain.

Drought, heat, and urban outbreaks

Statistical analyses in North America and Europe have found that large _Culex_-borne West Nile virus outbreaks are often associated with warm summers and with drought or low precipitation in the preceding months, even though many mosquito species increase after heavy rain. Proposed mechanisms, which are hypotheses at varying levels of support, include:

• Heavy rain can flush larvae out of catch basins, whereas drought leaves stagnant, nutrient-rich water that favors Cx. pipiens and Cx. quinquefasciatus.
• Drying of ponds can eliminate aquatic predators, so that the mosquitoes that colonize remaining water face less predation.
• Birds and mosquitoes congregate near scarce water, which raises contact rates.
• Stress during drought may weaken avian immunity and prolong or raise viremia.

Warming, altered precipitation, and land-use change are reshaping the distribution of _Culex_-borne disease. Some of the best documented developments are summarized below, and surveillance numbers change each season, so recent figures should be checked against current ECDC, CDC, and WHO reports.

• Europe: West Nile virus (lineages 1 and 2) and Usutu virus are now established in parts of southern and central Europe and have spread northward. The 2018 season was exceptional, with about 2,000 locally acquired human cases and about 180 deaths reported in Europe and neighboring countries. West Nile virus was detected in birds and horses in Germany in 2018 and in the first autochthonous human cases there in 2019. The first Dutch detections occurred in 2020. Italy (especially the Po Valley), Greece, Spain, Romania, Hungary, and other countries have reported large seasons in recent years.
• North America: West Nile virus has been detected in all 48 contiguous states and in the southern Canadian provinces. Over 50,000 human cases have been reported since 1999, and modeling suggests the true number of infections is several million. Large outbreaks include Maricopa County, Arizona, in 2021, with roughly 1,500 cases and about 100 deaths statewide.
• Asia: Reports from the Himalayan region describe Cx. tritaeniorhynchus and JEV at higher elevations than previously recognized, including in Tibet and in hill districts of Nepal, although the role of warming relative to improved surveillance is difficult to separate.
• Australia: JEV, formerly limited to the far north, was detected across southeastern Australia in early 2022, with infections in pigs at many piggeries and dozens of human cases including several deaths. The outbreak coincided with extensive flooding associated with La Niña conditions and the movement of waterbirds, and Cx. annulirostris is considered the main vector. Virus activity has been detected in later seasons.
• Hawaii: Warming is allowing mosquitoes and avian malaria to reach elevations that previously acted as refuges for native birds. The ʻakikiki on Kauaʻi has declined from several hundred individuals in the early 2010s to only a handful in recent surveys, and other species such as the kiwikiu and ʻākohekohe on Maui are also threatened.

Because human cases of _Culex_-borne WNV, SLEV, and JEV reflect earlier amplification in birds or pigs, public health agencies monitor mosquitoes, birds, and sentinel animals to detect transmission early. Standard methods include:

• Trapping: CDC miniature light traps baited with CO₂ capture host-seeking females. CDC gravid traps, baited with fermented organic infusions, attract females seeking oviposition sites. A high proportion of gravid-trap captures have already taken a blood meal, so infection rates in gravid traps are often higher.
• Pooled testing: Female mosquitoes are sorted by species into pools of typically 25 to 50 and tested by RT-qPCR. The minimum infection rate (MIR) is the number of positive pools divided by the total number of mosquitoes tested, multiplied by 1,000. It tends to underestimate prevalence when several infected mosquitoes occur in a pool. For M pools of equal size s with Y positive pools, the maximum likelihood estimate of infection prevalence is:

• Vector index: The vector index (VI) combines abundance and infection, summing over competent species i:

where N_i is the mean number of females of species i per trap-night and P_i is the estimated infection prevalence. It estimates the number of infected mosquitoes collected per trap-night. Programs use local threshold values (often in the range of 0.5 to 1) to trigger intensified control, and human cases commonly follow high values after a delay of one to a few weeks, although the relationship varies among sites.

• Other sources: Dead-bird reports, sentinel chickens, equine cases, and human case surveillance complement mosquito data.

Culex larvae often develop in water exposed to agricultural and urban insecticide runoff, and Culex species are a classic model for the evolution of insecticide resistance. Major mechanisms include:

Integrated vector management

Control of Culex populations combines reduction of larval habitat, larviciding, adulticiding when risk is high, and surveillance:

• Larval habitat management: Sealing or maintaining catch basins, improving drainage, covering latrines and septic tanks, and managing irrigation and wastewater. In some settings, layers of expanded polystyrene beads on pit latrines and cesspits suppress Cx. quinquefasciatus by preventing oviposition and by blocking larval respiration.
• Larvicides: Sustained-release formulations of Bti and L. sphaericus in catch basins, as well as spinosad and insect growth regulators such as methoprene and pyriproxyfen.
• Adulticiding: Ultra-low-volume (ULV) aerosol applications of pyrethroids (often with piperonyl butoxide) or organophosphates, usually at night when Culex are active. They are generally reserved for situations in which surveillance indicates an elevated risk to humans. Evaluations of aerial spraying during outbreaks have reported lower human case incidence in treated areas, although these comparisons are observational.
• Rice cultivation: Alternate wetting and drying of irrigated rice can reduce the aquatic habitat of Cx. tritaeniorhynchus and also reduces methane emissions from paddies. The size of the mosquito effect varies with local conditions, and fish stocking in rice-fish systems adds a biological control component.

_Wolbachia_-based approaches

Strains of Wolbachia that differ in cytoplasmic incompatibility (CI) can be exploited for Culex population suppression. In 1967 Hannes Laven reported the local elimination of Cx. quinquefasciatus from a village in Myanmar by releasing males that were incompatible with the resident females, an early demonstration of the incompatible insect technique. The _w_Pip lineage of Wolbachia has diversified into several groups with different sets of CI factor genes, which produces complex patterns of compatibility among mosquito populations.

In Hawaii, a program known as "Birds, Not Mosquitoes" began releasing incompatible male Cx. quinquefasciatus from helicopters over forest areas of Maui in late 2023, with the aim of suppressing mosquito populations and protecting remaining honeycreepers from avian malaria. The program is expanding and being evaluated, and its long-term effectiveness has not yet been established.

Vaccines and drug-based approaches

Medical countermeasures complement Culex vector control across human and veterinary populations:

• Japanese encephalitis: Because JEV cannot be eliminated from its pig-bird transmission cycle, human vaccination is the central strategy in endemic countries. Several vaccine types are in use, including the live-attenuated SA 14-14-2 vaccine, a live chimeric vaccine built on the yellow fever 17D backbone (IMOJEV), and inactivated Vero cell-derived vaccines (such as IXIARO, marketed as JESPECT in some countries, and others).
• West Nile virus: Licensed vaccines exist for horses (inactivated, recombinant canarypox-vectored, and chimeric types), but no human vaccine is licensed. Several candidates have been tested in early-phase trials.
• Lymphatic filariasis: The Global Programme to Eliminate Lymphatic Filariasis relies on mass drug administration. Regimens include the triple-drug combination of ivermectin, diethylcarbamazine, and albendazole, which clears microfilariae from the blood for a prolonged period and so reduces transmission to mosquitoes. About twenty countries have been validated by the WHO as having eliminated the disease as a public health problem.

Why do *Culex* mosquitoes drive late-summer West Nile virus spillover to humans?

Temperate *Culex* vectors such as *Culex pipiens* and *Culex tarsalis* feed preferentially on passerine birds (notably American robins) during spring and early summer, amplifying West Nile virus within the avian reservoir community. In late summer, as preferred avian hosts disperse after nesting and hybrid *pipiens*–*molestus* mosquitoes take a larger fraction of mammalian blood meals, infectious females shift toward biting humans and horses, driving the late-summer peak in neuroinvasive spillover.

How does the *Culex pipiens* form *molestus* differ biologically from form *pipiens*?

Within the *Culex pipiens* complex, form *pipiens* is an above-ground, eurygamous ecotype that requires open swarms to mate, depends on avian blood meals for every egg batch (anautogeny), and enters photoperiodic winter diapause. By contrast, form *molestus* occupies subterranean habitats such as subways and sewers, mates in confined spaces (stenogamy), matures its first egg raft without a blood meal using larval reserves (autogeny), bites mammals readily, and remains active year-round without diapause.

How did esterase gene amplification evolve and spread in *Culex* populations worldwide?

In *Culex pipiens* and *Culex quinquefasciatus*, intensive organophosphate larviciding selected for tandem gene duplications at the *Ester* locus, amplifying the carboxylesterase genes *Est-2* and *Est-3* up to 80–100 copies per haploid genome. The overproduced esterase enzymes account for up to 10% of total soluble protein in resistant mosquitoes, stoichiometrically binding and sequestering organophosphate molecules before they can inhibit synaptic acetylcholinesterase.

• West Nile virus
• Japanese encephalitis
• Lymphatic filariasis
• Mosquito-borne disease
• Vector control
• Wolbachia