Aedes aegypti vectorial capacity is determined by the infecting genotype of dengue virus

Abstract

Dengue viruses causing severe, hemorrhagic disease have displaced less virulent strains in the Americas during the past three decades. The American (AM) genotype of dengue serotype 2 has been endemic in the Western Hemisphere and South Pacific, causing outbreaks of dengue fever (DF), but has not been linked to dengue hemorrhagic fever (DHF). The Southeast Asian (SEA) genotype of dengue was introduced into this hemisphere in 1981, has caused outbreaks with numerous cases of DHF, and has displaced the AM genotype in several countries. We investigated the effect of viral genotype on the potential for transmission by infecting Aedes aegypti mosquitoes collected in South Texas with six viruses, representing these two genotypes. Viral replication in the midgut was significantly higher in SEA-infected mosquitoes, and virus-specific proteins could be detected in salivary glands 7 days earlier in SEA- than AM-infected mosquitoes. This much earlier appearance of dengue virus in salivary glands resulted in an estimated 2- to 65-fold increase in the vectorial capacity of these mosquitoes for the viruses that can cause DHF. This may be one of the mechanisms through which more virulent flaviviruses spread and displace others globally.

FIGURE 1

Infection rates for (A) midguts and (B) salivary glands of Aedes aegypti females singly infected with each of three Southeast Asian or American genotype dengue 2 viruses. Six to ten individuals per virus strain were examined at each time point. Error bars represent the standard error of the mean from three virus strains for each genotype. SEA, Southeast Asian genotype; AM, American genotype; MG, midgut; SG, salivary glands.

FIGURE 2

Comparison of regression lines for DENV-2 infections of Aedes aegypti midguts (A) and salivary glands (B) by three strains each of Southeast Asian (SEA; solid squares, solid line) or American (AM; open circles, dashed line) origin. On the y-axis, the logit represents ln (total number infected/total number uninfected) for each genotype. In midguts (A), both the slope and intercept differ significantly between genotypes (P < 0.05). In salivary glands (B), only the intercepts differ significantly (P < 0.05).

FIGURE 3

(A) Viral RNA quantities in midguts of Aedes aegypti females singly infected with each of three Southeast Asian or three American genotype dengue 2 viruses. Six to ten individuals for each of six virus strains were examined at each time point, for day 1–14 P.I. (B) For time points 1, 4, and 12 hr, six individuals were examined for each of two virus strains. Asterisks indicate times at which differences are significant by unpaired t test. Error bars represent the standard error of the mean. SEA, Southeast Asian genotype; AM, American genotype.

FIGURE 4

Likelihood of an infected mosquito surviving the extrinsic incubation period (EIP) for Southeast Asian and American genotypes of dengue 2 virus. The probability of surviving the EIP, pⁿ, is plotted against the probability of daily survival, p. Values for p were obtained from the literature.-